1. What is a gene?
A gene is a sequence of DNA nucleotides that codifies the production of a protein.
Image Diversity: DNA molecule
2. Is a gene a triplet of consecutive DNA nucleotides?
A gene is not a triplet of DNA nucleotides with their respective nitrogen-containing bases, like AAG or CGT. The nucleotide triplets may be pieces of genes but not genes.
A gene is a portion of a DNA molecule that codifies a specific protein. Thus it is formed by several DNA nucleotide triplets.
3. How is the concept of chromosome related to the concept of the gene?
A chromosome is a DNA molecule. A chromosome may contain several different genes and also DNA portions that are not genes.
Image Diversity: chromosome
4. What is meant by “gene locus”?
Gene locus (locus means place) is the location of a gene in a chromosome, i.e., the position of the gene in a DNA molecule.
Image Diversity: gene locus
5. What are alleles of a gene?
Diploid individuals have paired chromosomes. For example in humans there are 23 pairs of chromosomes totaling 46 chromosomes. Each pair comprehends homologous chromosomes, one chromosome from the father and another from the mother, both of them containing information related to the production of the same proteins (with the exception of the sex chromosomes, which are partially heterologous). So in the diploid individual it is said that each gene has two alleles, one in each chromosome of the homologous pair.
Image Diversity: alleles
6. Are the alleles of a gene necessarily originated one from the father and the other from the mother? Are there exceptions?
It is natural that alleles have come one from the father and the other from the mother but it is not obligatory. In a “clone” generated by nucleus transplantation technology, for example, the alleles come from a single individual. In polysomies (as in trisomy 21) each gene of the affected chromosome has three alleles, in trisomies, or four, in tetrasomies.
7. What is a phenotype?
A phenotype is every observable characteristic of a living being conditioned by its genes. Some phenotypes may be altered by nongenetic factors (for example, artificial hair coloring). Specific phenotypes are also called phenotypical traits.
8. What is a genotype? What is the difference between genotype and phenotype?
Genotype is the genes, DNA nucleotide sequences contained in the chromosomes of an individual, that condition the phenotype. Phenotypes then are a biological manifestation of genotypes.
For example, the altered hemoglobin chain of sickle cell disease and the manifestation of the disease itself are the phenotype. The altered DNA nucleotide sequence in the gene that codifies the production of that abnormal hemoglobin chain is the genotype.
9. Does the environment exert an influence on the phenotype?
A phenotype may be altered (compared to the original situation conditioned by its genotype) by nongenetic means. Examples: some hormones may cease to be secreted due to diseases but the genes that determine their secretion remain intact; a person can go to a hairdresser and change the color of his/her hair; plastic surgery can be performed to alter facial features of an individual; colored contact lenses may be worn; a plant can grow beyond its genetically conditioned size by application of phytohormones.
Revealing cases of environmental influence on phenotypes are observed in monozygotic twins that have grown in different places. Generally these twins present very distinct phenotypical features due to the environmental and cultural differences of the places where they lived and to their different individual experiences in life.
(Biologically programmed phenotypical changes, like nonpathological changes of the skin color caused by sunlight exposure, tanning, or the variation ofthe color of some flowers according to the pH of the soil cannot be considered independent from the genotype. Actually these changes are planned by the genotype as natural adaptations to environmental changes.)
10. Are environmental phenotypical changes transmitted to the offspring?
Changes caused on phenotypes by the environment are not transmitted to the offspring (unless their primary cause is genotypical change in germ cells or in gametic cells). If a person changesthe color of the hair or undergoes aesthetic plastic surgery the resulting features are not transmitted to his/her offspring.
11. What are the situations in which the environment can alter the genotype of an individual? What is the condition for this type of change to be transmitted to the offspring?
The environment can only alter genotypes when its action causes alterations in the genetic material (mutations) of the individual, i.e., deletion, addition or substitution of entire chromosomes or of nucleotides that form the DNA molecules.
Mutations are only transmitted to the offspring when affecting the germ cells that produce gametes or the gametes themselves.
12. What are some examples of phenotypical characteristics that present two or more varieties and of phenotypical features that do not vary? In relation to the genes correspondent to those characteristics that vary among individuals what can be expected about their alleles?
Color of the eyes, color of the hair, color of the skin, height, blood type are examples of phenotypical features that present two or more varieties. Other examples arethe color of flowers and seeds in some plants, the sex of the individual in dioecius species, etc. Examples of phenotypical characteristics that do not present variation among individuals of the same species are: in general the number of limbs, the anatomical position of the organs, the general constitution of tissues and cells, etc.
Phenotype possibility of presenting natural variations (in beings of the same species) are necessarily determined by two or more different alleles of the correspondent gene. These different alleles combine and form different genotypes that condition the different phenotypes (variations).
13. Considering a pair of homologous chromosomes containing a gene having two different alleles how many different genotypes can the individual present?
If a gene of a diploid species has different alleles, for example, A and A’, the possible genotypes are: A’A’, AA, and AA’. So any of these three different genotypes may be the genotype of an individual.
14. For an individual having a genotype formed of two different alleles that condition different varieties of the same phenotypical trait, upon what will the phenotypical feature actually manifested depend?
If an individual presents a gene having different alleles (common situation), for example, A and A’, three types of genotypes may be formed: AA, A’A’ and AA’. The question refers to an individual bearing a genotype made of two different alleles, so it is the AA’ genotype (the heterozygous individual).
This AA’ individual may manifest the phenotype conditioned by the allele A or the phenotype conditioned by the allele A’ or still a mixed phenotype of those two forms. If the allele A is dominant over the allele A’ the form conditioned by A will manifest. If A’ is the dominant allele, the form determined by A’ will manifest. This phenomenon is known as dominance and occurs because the recessive (nondominant) allele manifests only when present in double in the genotype (in homozygosity), while the dominant allele manifests even when in heterozygosity. If none of the alleles dominate a mixture of the two varieties conditioned by both alleles appears or instead a third form may come out.
15. What is the difference between dominant allele and recessive allele?
Dominant allele is the allele that determines phenotypical features that manifest in homozygous or heterozygous genotypes.
In Genetics the dominant allele is represented in uppercase, e.g., “A”, and its recessive allele is written in lowercase, “a”.
In molecular terms generally the recessive allele has a nucleotide sequence previously identical to the corresponding sequence in the dominant allele but that during evolution was inactivated by mutation. This fact explains the expression of the dominant phenotype in heterozygosity (since one functional allele is still present).
16. Whenever a pair of alleles has different alleles is there dominance between them?
Not in all cases of a gene having two different alleles is the dominance complete. There are genes in which heterozygosity occurs with incomplete dominance (manifestation of an intermediate phenotype in relation to the homozygous, like in the color of roses, between white and red) and other genes that present codominance (expression of a third different feature, as in the MN blood group system).
17. What is the difference between homozygosity and heterozygosity?
Homozygosity occurs when an individual has two identical alleles of a gene, for example, AA or aa. Heterozygosity occurs when an individual has two different alleles of the same gene, in the example, Aa.
18. Why can it be said that a recessive allele can remain hidden in the phenotype of an individual and revealed only when manifested in homozygosity in the offspring?
A recessive allele can remain hidden because it does not manifest in heterozygous individual, i.e., it may be present in the genotype but not expressed in the phenotype. When this allele is transmitted to the offspring and forms homozygous genotype with another recessive allele from other chromosomal lineage the phenotypical characteristics that come out reveal its existence.
1. Who was Gregor Mendel?
Mendel is considered the father of Genetics. He was a monk, biologist and botanist born in Austria in 1822 and who died in 1884. During the years 1853 to 1863 he cultivated pea plants in the gardens of his monastery to be used in his research. His experiments consisted of crossing pea plants of distinct characteristics (size, color of the seeds, etc.), cataloging the results and interpreting them. The experiments led him to enunciate his laws, results published in 1886 with no scientific repercussion at that time. Only at the beginning of the 20th century, in 1902, 18 years after his death, were his merits broadly recognized.
Image Diversity: the father of Genetics Mendel's laws
2. What in Genetics is hybridization?
Hybridization in Genetics is the crossing of individuals from “pure” and different lineages in relation to a given trait, i.e., the crossing of different homozygous for the studied trait.
In Mendel’s experiments with peas, for example, a plant from a green pea lineage obtained from self fecundation of its ascendants through several generations was crossed (cross fecundation) with another plant from a yellow lineage also obtained by self fecundation ofascendants. (The self fecundation through several generations of ascendants and the exclusive obtainment of individuals with the desired characteristics ensured that the individuals of the parental generation were “pure”, i.e., homozygous for that characteristic.)
3. What is monohybridism?
Monohybridism is the study of only one characteristic in the crossing of two pure individuals (hybridization) for that characteristic.
4. Considering hybridization in a trait like the color of the flowers of a given plant species (red dominant/ yellow recessive) conditioned by a pair of different alleles, what are the phenotypical results of the first generation (F1) and the phenotypical results of the second generation (F2, formed by crossing among F1 genotypes)? What are the phenotypical proportions in F1 and F2?
In relation to genotypes and phenotypes the hybridization comprises of: parental generation (P): RR (read), yy (yellow). F1 generation (RR x yy): Ry (red). F2 generation (Ry x Ry): RR (red), Ry (red), Ry (red) and yy (yellow).
In the F1 generation the proportion of red flowers is 100%. In the F2 generation, the phenotypical proportion is three red (75%) to one yellow (25%).
5. Considering hybridization in a trait like the color of the flowers of a given plant species (red/yellow) conditioned by a pair of different alleles in relation to complete dominance (red dominant/ yellow recessive), why in the F1 generation is one of the colors missing?
In this monohybridism one of the colors does not appear in the F1 generation because their parental generators are pure, i.e., homozygous, and in F1 all descendants are heterozygous (each parental individual forms only one type of gamete). Since only heterozygous genotypes appear and red is dominant over yellow the individuals of the F1 generation will present only red flowers.
6. Considering hybridization in a given trait like the color of the hair of a mammalian species (white/black) conditioned by a pair of different alleles under complete dominance (black dominant, B/ white recessive, w), how can the phenotypical proportion obtained in the F2 generation be explained? What is this proportion?
In the monohybridism conditioned by two different alleles the F1 generation presents only heterozygous individuals (Bw). In F2 there is one individual BB, two individuals Bw and one individual ww. In relation to the phenotype there are in F2 two black individuals and one white individual, since black is the dominant color. So the proportion is 3:1, three black-haired to one white-haired.
7. What is meant by saying that in relation to a given trait conditioned by a gene with two different alleles the gametes are always “pure”?
To say that gametes are pure means that they always carry only one allele of the referred trait. Gametes are always “pure” because in them the chromosomes are not homologous, they contain only one chromosome of each type.
8. What is the Mendel’s first law?
The Mendel’s first law postulates that a characteristic (trait) of an individual is always determined by two factors, one inherited from the father and the other from the mother and the direct offspring of the individual receives from it only one of these factors (aleatory). In other words, each trait is determined by two factors that segregate during gamete formation.
The Mendel’s first law is also known as the law of purity of gametes. Mendel deduced the way genes and alleles were transmitted and traits were conditioned without even knowing of the existence of these elements.
9. Which is the type of gamete (for a given trait) produced by a dominant homozygous individual? What is the genotypical proportion of these gametes? What about a recessive homozygous individual?
If an individual is dominant homozygous, for example, AA, it will produce only gametes having the allele A. The proportion thus is 100% of AA gametes.
If an individual is recessive homozygous, for example, aa, it will produce only gametes having the allele a, also in a 100% proportion.
10. Which is the type of gamete produced by a heterozygous individual? What is the genotypical proportion of these gametes?
Heterozygous individuals, for example, AA, produce two different types of gametes: one containing the allele A and another type containing the allele a. The proportion is 1:1.
11. In the F2 generation of a hybridization for a given trait conditioned by a pair of alleles T and t, according to Mendel’s first law what are the genotypes of each phenotypical form? How many respectively are the genotypical and phenotypical forms?
In the mentioned hybridization the genotypical forms in F2 will be TT, tt and Tt. Therefore there will be three different genotypical forms and two different phenotypical forms (considering T dominant over t).
12. Why can the crossing of an individual that manifests dominant phenotype with another that manifests recessive phenotype (for the same trait) determine whether the dominant individual is homozygous or heterozygous?
From the crossing of an individual having recessive phenotype with another having dominant phenotype (for the same trait) it is possible to determine whether the dominant individual is homozygous or heterozygous. This is true because the genotype of the recessive individual is obligatorily homozygous, for example, aa. If the other individual is also homozygous, AA, the F1 offspring will be only heterozygous (aa x AA = only Aa). If the other individual is heterozygous there will be two different genotypical forms, Aa and aa in the 1:1 proportion. So if a recessive phenotype appears in the direct offspring the parental individual that manifests dominant phenotype is certainly heterozygous.
13. What is a genetic family tree?
Genetic family tree is a schematic family tree that shows the biological inheritance of some trait through successive generations.
Genetic family trees are useful because it is practically impossible and ethically unacceptable to make experimental crossings for genetic testing between human beings. With the help of family tress the study is made by analysis of marriages (and crossings) that have already occurred in the past. From the analysis of family trees, for example, information on probabilities of the emergence of some phenotype and genotypes (including genetic diseases) in the offspring of a couple can be obtained.
Image Diversity: genetic family tree
14. What are the main conventional symbols and signs used in genetic family trees?
In genetic family trees the male sex is usually represented by a square and the female by a circle. Crossings are indicated by horizontal lines that connect squares to circles and their direct offspring are listed below and connected to that line. The presence of the studied phenotypical form is indicated by a complete hachure (shading) of the circle or the square correspondent to the affected individual. It is useful to enumerate the individuals from left to right and from top to bottom for easy reference.
15. What are the three main steps for a good study of a genetic family tree?
Step 1: to determine whether the studied phenotypical form has a dominant or recessive pattern. Step 2: to identify recessive homozygous individuals. Step 3: to identify the remaining genotypes.
16. What is Mendel’s second law?
Mendel’s second law postulates that two or more different traits are also conditioned by two or more pair of different factors and that each inherited pair separates independently from the others. In other words, gametes are formed always with an aleatory representative of each pair of the factors that determine phenotypical characteristics.
Mendel’s second law is also known as the law of independent segregation of factors, or law of independent assortment.
17. What is the condition for Mendel’s second law to be valid?
Mendel’s second law is only valid for genes located in different chromosomes. For genes situated in the same chromosome, i.e., linked genes (genes in linkage) the law is not valid since the segregation of these genes is not independent.
18. According to Mendel’s second law, in the crossing between homozygous individuals concerning two pairs of nonlinked alleles, AABB x aaBB, what are the genotypical and phenotypical proportions in F1 and F2?
Parental genotypes: AABB, aaBB. Gametes from the parental generation: Ab and aB. Thus F1 will present 100% AaBb gametes (and the phenotypical correspondent form).
As F1 are AaBb individuals the gametes from their crossing can be: AB, Ab, aB and ab. The casual combination of these gametes forms the following genotypical forms: one AABB, two AABb, two AaBb, four AaBB, one Aabb, one Aabb, one aaBB, two aaBb and two aabb. The phenotypical proportion then would be: nine A_B_ (double dominant); three A_bb (dominant for the first pair, recessive for the second); three aaB_ (recessive for the first pair, dominant for the second); one aabb (double recessive).
19. Considering independent segregation of all factors, how many types of gametes does a VvXXWwYyzz individual produce? What is the formula to determinate such number?
The mentioned individual will produce eight different types of gametes (attention, gametes and not zygotes).
To determine the number of different gametes produced by a given multiple genotype the number of heterezygous pairs is counted (in the mentioned case, three) and the result is placed as an exponent of two (in the example, 2.2.2 = 8).
20. How is it possible to obtain the probability of emergence of a given genotype formed of more than one pair of different alleles with independent segregation from the knowledge of the parental genotypes?
Taking as example the crossing of AaBbCc with aaBBCc, for each considered pair of allele it is possible to verify which genotypes it can form (as in an independent analysis) and in which proportion. AA x aa: Aa, aa (1:1). Bb x BB: BB, Bb (1:1). Cc x Cc: CC, Cc, cc (1:2:1). The genotype to which the probability is to be determined is for example aaBbcc. For each pair of this genotype the formation probability is determined: to aa, 0.5; to Bb, 0.5; to cc, 0.25. The final result is obtained by multiplication of these partial probabilities, 0.5 x 0.5 x, 0.5, resulting 0.0625.
Review of Epistasis and
Other Non-Mendelian Inheritances
1. According to Mendel’s law phenotypical characteristics would be determined by pair of factors (alleles) that separate independently in gametes. What are the main types of inheritances that are exceptions to Mendel’s rules?
There are many types of inheritance that do not follow the mendelian pattern. Notable among them are: multiple alleles, gene interactions (complementary genes, epistasis and quantitative, or polygenic, inheritance), linkage with or without crossing over and sex-linked inheritance.
Pleiotropy, lacking of dominance and lethal genes do not fit as variations of inheritance since genes can have these behaviors and at the same time obey mendelian laws.
Mutations and aneuploidies are abnormalities that also alter the mendelian pattern of inheritance as well as mitochondrial inheritance (passage of mitochondrial DNA from the mother through the cytoplasm of the egg cell to the offspring).
2. What is the genetic condition in which the heterozygous individual has different phenotype from the homozygous individual?
This condition is called lack of dominance and it can happen in two ways: incomplete dominance or codominance.
In incomplete dominance the heterozygous presents an intermediate phenotype between the two types of homozygous, as in sickle cell anemia in which the heterozygous produces some sick red blood cells and some normal red blood cells. Codominance occurs, for example, in the genetic determination of the MN blood group system, in which the heterozygous has a phenotype totally different from the homozygous, not being an intermediate form.
Image Diversity: incomplete dominance codominance
3. What is pleiotropy?
Pleiotropy (or pliotropy) is the phenomenon in which a single gene conditions several different phenotypical traits.
Some phenotypical traits may be sensitive to pleiotropic effects (for example, inhibition) of other genes, even when conditioned by a pair of alleles in simple dominance. In these cases a mixture of pleiotropy and gene interaction is characterized.
Image Diversity: pleiotropy
4. What are lethal genes?
Lethal genes are genes having at least one allele that, when present in the genotype of an individual, causes death. There are recessive lethal alleles and dominant lethal alleles. (There are also genes having alleles that are dominant when in heterozygosity but lethal when in homozygosity, i.e., the dominance related to the phenotype does not correspond to the dominance related to lethality.)
Image Diversity: lethal genes
5. What are multiple alleles? Is there dominance in multiple alleles?
Multiple alleles is the phenomenon in which the same gene has more than two different alleles (in normal mendelian inheritance the gene has only two alleles). Obviously these alleles combine in pairs to form the genotypes.
In multiple alleles relative dominance among the alleles may exist. A typical example of multiple alleles is the inheritance of the ABO blood group system, in which there are three alleles (A, B or O, or IA, IB and i). IA is dominant over i, which is recessive in relation to the other IB allele. IA and IB lack dominance between themselves.
Another example is the color of rabbit fur, conditioned by four different alleles (C, Cch, Ch and c). In this case the dominance relations are C > Cch > Ch > c (the symbol > means “dominates over”).
Image Diversity: multiple alleles
6. What are gene interactions? What are the three main types of gene interactions?
Gene interaction is the phenomenon in which a given phenotypical trait is conditioned by two or more genes (do not confuse with multiple alleles in which there is a single gene having three or more alleles).
The three main types of gene interaction are: complementary genes, epistasis and polygenic inheritance (or quantitative inheritance).
7. What are complementary genes? Does this inheritance pattern obey Mendel’s second law?
Complementary genes are different genes that act together to determine a given phenotypical trait.
For example, consider a phenotypical trait conditioned by 2 complementary genes whose alleles are respectively X, x, Y and y. Performing hybridization in F2 4 different phenotypical forms are obtained: X_Y_ (double dominant), X_yy (dominant for the first pair, recessive for the second), xxY_ (recessive for the first pair, dominant for the second) and xxyy (double recessive). This is what happens, for example, regarding the color of budgerigar feathers, in which the double dominant interaction results in green feathers, the dominant for the first pair, recessive for the second interaction results in yellow feathers, the recessive for the first pair, dominant for the second interaction leads to blue feathers and the double recessive interaction leads to white feathers.
Each complementary gene segregates independently from the others since they are located in different chromosomes. Therefore the pattern follows Mendel’s second law (although it does not obey Mendel’s first law).
Image Diversity: complementary genes
8. What is epistasis? What is the difference between dominant epistasis and recessive epistasis?
Epistasis is the gene interaction in which a gene (the epistatic gene) can disallow the phenotypical manifestation of another gene (the hypostatic gene). In dominantepistasis the inhibitor allele is the dominant allele (for example, I) of the epistatic gene so inhibition occurs in dominant homozygosity (II) or in heterozygosity (Ii). In recessiveepistasis the inhibitor allele is the recessive allele of the epistatic gene (i) so inhibition occurs only in recessive homozygosity (ii).
Image Diversity: epistasis
9. In the hybridization of 2 genes (4 different alleles, 2 of each pair) how does epistasis affect the proportion of phenotypical forms in the F2 generation?
In dihybridism without epistasis double heterozygous parental individuals cross and in F2 4 phenotypical forms appear. The proportion is 9 double dominant to 3 dominant for the first pair, recessive for the second to 3 recessive for the first pair, dominant for the second to 1 double recessive (9:3:3:1).
Considering that the epistatic gene is the second pair and that the recessive genotype of the hypostatic gene means lacking of the characteristic, in the F2 generation of the dominantepistasis the following phenotypical forms would emerge: 13 dominant for the second pair or recessive for the first, i.e., the characteristic does not manifest, 3 dominant for the first pair, recessive for the second, i.e., the characteristic manifests. The phenotypical proportion would be 13:3. In the recessiveepistasis in F2 the phenotypical forms that would emerge are: 9 double dominant (the characteristic manifests), 7 recessive for the first pair or recessive for the second, i.e., the characteristic does not manifest. So the phenotypical proportion would be 9:7.
These examples show how epistasis changes phenotypical forms and proportions, from the normal 9:3:3:1 in F2 to 13:3 in dominant epistasis or to 9:7 in recessive epistasis (note that some forms have even disappeared).
(If the recessive genotype of the hypostatic gene is active, not simply meaning that the dominant allele does not manifest, the number of phenotypical forms in F2 changes.)
10. What is polygenic inheritance? How does it work?
Polygenic inheritance, also known as quantitative inheritance, is the gene interaction in which a given trait is conditioned by several different genes having alleles that may or may not contribute to increase the phenotype intensity. The alleles may be contributing or noncontributing and there is no dominance among them. Polygenic inheritance is the type of inheritance, for example, of skin color and of stature in humans.
Considering a given species of animal in which the length of the individual is conditioned by polygenic inheritance of three genes, for the genotype having only noncontributing alleles (aabbcc) a basal phenotype, for example, 30 cm, would emerge. Considering also that for each contributing allele a 5 cm increase in the length of the animal is added, so in the genotype having only contributing alleles (AABBCC) the animal would present the basal phenotype (30 cm) plus 30 cm more added by each contributing allele, i.e., its length would be 60 cm. In the case of triple heterozygosity, for example, the length of the animal would be 45 cm. That is the way polygenic inheritance works.
Image Diversity: polygenic inheritance
11. What is the most probable inheritance pattern of a trait with gaussian proportional distribution of phenotypical forms?
If a trait statistically has a normal (gaussian, bell-shaped curve) distribution of its phenotypical forms it is probable that it is conditioned by polygenic inheritance (quantitative inheritance).
In quantitative inheritance the effects of several genes add to others making it possible to represent the trait variation of a given population in a gaussian curve with the heterozygous genotypes in the center, i.e., appearing in larger number, and the homozygous in the extremities.
12. How to find the number of pair of alleles involved in polygenic inheritance using the number of phenotypical forms of the trait they condition?
Considering “p” the number of phenotypical forms and “a” the number of involved alleles of the polygenic inheritance. The formula p = 2a + 1 is then applied.
(Many times it is not possible to determine precisely the number of phenotypical forms, p, due to the multigenic feature of the inheritance, since often the observed variation of phenotypes seems to be on a continuum or the trait suffers environmental influence.)
13. Why is sex-linked inheritance an example of nonmendelian inheritance?
Sex-linked inheritance is a type of nonmendelian inheritance because it opposes Mendel’s first law, which postulates that each trait is always conditioned by two factors (alleles). In nonhomologous regions of the sex chromosomes the genotypes of the genes contain only one allele (even in the case of the XX karyotype, i.e., in women, one of the X chromosomes is inactive).
Image Diversity: sex-linked inheritance
14. What is mitochondrial inheritance?
Mitochondrial inheritance is the passage of mitochondrial DNA molecules (mtDNA) to the offspring. All stock of mtDNA an individual has have come from the mother, the maternal grandmother, the maternal great grandmother and so on, since mitochondria are inherited from the cytoplasm of the egg cell (that later constitutes the cytoplasm of the zygote).
There are several genetic diseases caused by mitochondrial inheritance, like Leber's hereditary optic neuropathy, that leads to loss of the central vision of both eyes, and the Kearns-Sayre syndrome, a neuromuscular disease that causes ophthalmoplegia and muscle fatigue.
Mitochondrial inheritance is an excellent means of genetic analysis of the maternal lineage (just like the Y chromosome is an excellent means of study of the paternal lineage).
Image Diversity: mitochondrial inheritance
Easily Learn Crossing Over and Linkage
1. Why is not Mendel’s second law always valid for two or more phenotypical traits of an individual?
Mendel’s second law, or the law of the independent assortment, is valid for genes located in different chromosomes. These genes during meiosis segregate independently.
Mendel’s second law however is not valid for phenotypical features conditioned by genes located in the same chromosome (genes under linkage), since these genes, known as linked genes, do not separate in meiosis (except for the phenomenon of crossing over).
Image Diversity: genetic linkage
2. Why is drosophila a convenient animal for the study of linked genes?
The fruit fly drosophila is suitable for the study of Genetics because it presents many distinct traits but only four chromosomes (one sexchromosome and three autosomes).
Image Diversity: drosophila karyotype
3. What is linkage?
Two genes are said to be under linkage, or linked, when they reside in the same chromosome.
For example, the research of the human genome discovered that the factor III of clotting gene and the factor V of clotting gene are located in the samechromosome (the human chromosome 1). The factor VII gene however is not linked to those genes since it is located in the chromosome 13.
4. What is crossing over? How is meiosis related to this phenomenon?
Linked alleles, for example, A-b and a-B, form the gametes A-b and a-B that maintain the linkage of the alleles. This type of linkage is called complete linkage. In the first division of meiosis (meiosis I) however the crossing over phenomenon may occur. Chromosomes from a pair of homologous may exchange extremities and some once linked alleles, for example, A-b and a-B, recombine to form different gametes, in the case, A-B and a-b.
Crossing over may happen when the arms of the chromatids of each homologous are paired during meiosis. Matching portions of the extremities of two nonsister chromatids (one from one homologous of the pair) break and the pieces are exchanged, each of them becoming part of the arm of the other chromatid. For example, if the allele A is situated in a side of the arm relating to the point of breaking and the allele b is located in the other side, they will be separated and gametes A-B and a-b will be formed, instead of A-b and a-B.
(The percentage of recombinant gametes relating to normal gametes depends upon the crossing over rate that in its turn depends upon how far distant the given alleles are in the chromosome.)
Image Diversity: crossing over
5. In genetic recombination by crossing over what is the difference between parental gametes and recombinant gametes?
Parental gametes are those gametes that maintain the original linkage of genes (alleles) in the chromosome. Recombinant gametes are those in which the original linkage is undone due to exchange of chromosomal pieces by crossing over during meiosis.
6. What is recombination frequency?
Recombination frequency, or crossing over rate, is the percentage of recombinant gametes made by crossing over (in relation to the number of parental gametes made). It always refers to two genes located in the same chromosome.
Image Diversity: recombination frequency
7. Why does the recombination frequency of genes vary with the distance between them in the chromosome?
The farther the distance between the loci of two genes in a chromosome the higher the recombination frequency between these genes. This is true because once alleles are nearer in the chromosome it is more probable that they are kept united when chromosomal extremities are exchanged by crossing over. On the other hand, if they are farther apart it will be easier for them to separate by crossing over.
8. What is a centimorgan?
Centimorgan, or recombination unit, by convention is a distance between two linked genes that corresponds to 1% of recombination frequency of these genes.
9. How can the concept of recombination frequency be used in genetic mapping?
Genetic mapping is the determination of the location of the genes in a chromosome.
By determining the recombination frequency between several different linked genes it is possible to estimate the distance between them in thechromosome . For example, if a gene A has a recombination frequency of 20% with the gene B, this gene B has recombination frequency of 5% with the gene C and this gene C has recombination frequency of 15% with the gene A, it is possible to assert that the gene A is 20 centimorgans distant from the gene B and that between them lies the gene C at 15 centimorgans of distance from the gene A.
Image Diversity: genetic mapping
10. Is crossing over important for the diversity of biological evolution?
Sexual reproduction and recombination of linked genes (crossing over) are, along with mutations, the main instruments of biological variability. Sexual reproduction allows many combinations between genes situated in different chromosomes.Crossing over, however, is the only means to provide recombination of alleles located in a same chromosome. Crossing over probably emerged and has been maintained by the evolution because of its importance to biological diversity.
Sex Determination and Sex-linked Inheritance
1. How is the genetic determination of sex established in humans?
In the diploid genome of human beings there are 46 chromosomes, 44 of them are autosomes and two are sex chromosomes. The individual inherits one of these chromosomes from each parent.
The human sex chromosomes are called X chromosome and Y chromosome. Individuals having two X chromosomes (44 + XX) are female. Individuals having one X chromosome and one Y chromosome (44 + XY) are male. (Individuals 44 + YY do not exist since the chromosome Y is exclusively from paternal lineage.)
Image Diversity: human karyotype sex chromosomes
2. What are the homologous and the heterologous portions of the human sex chromosomes?
Homologous portion is that in which there are genes having alleles in both Y and X sex chromosomes. The homologous portions are situated more in the central part of the sex chromosomes, near the centromere.
Heterologous portion is that whose genes do not have correspondent alleles in the other sex chromosome. These genes are located more in the peripheral regions of the arms of the Y and X chromosomes.
3. Concerning the sex chromosomes of the XY system which type of gamete do the male and the female individuals respectively produce?
The individual of the male sex is XY so he forms gametes containing either the X chromosome or the Y chromosome in a 1:1 proportion. The individual of the female sex is XX and thus she forms only gametes containing an X chromosome.
4. Is it possible that an X chromosome of a woman can have come from her father?
It is not only possible that an X chromosome of a woman is from her father, it is certain. Every woman has an X chromosome from her father and the other X chromosome from her mother.
In men however the X chromosome comes always from his mother and the Y chromosome is always from his father.
5. Is it more indicated for a geneticist desiring to map the X chromosome of the mother of a given family (the researcher does not have access to her DNA, only access to the genetic material of the offspring) to analyze the chromosomes of her daughters or of her sons?
To analyze the X DNA of a mother (assuming no access to her own material) it is more indicated to study the genetic material of her sons since all X chromosomes of males come fromthe mother while the daughters have X chromosomes from the mother and from the father. By researching the material of the sons it is ensured that the studied X chromosome is from the mother.
6. Do the genes of the X and Y chromosomes determine only sex characteristics?
Besides sex genes the sex chromosomes have also autosomal genes, genes that codify several proteins related to nonsexual traits.
7. What are the main diseases caused by errors of the number of sex chromosomes in the cells of an individual?
Diseases caused by abnormal number of sex chromosomes are called sex aneuploidies.
The main sex aneuploidies are: 44 + XXX, or trisomy X (women whose cells have an additional X chromosome); 44 + XXY, or Klinefelter's syndrome (men whose cells have an extra X chromosome); 44 + XYY, or double Y syndrome (men whose cells have an additional Y chromosome); 44 + X, Turner’s syndrome (women whose cells lack an X chromosome).
8. What is the inactivation of the X chromosome? What is a Barr body?
Inactivation of the X chromosome is a phenomenon that occurs in women. Since women have two X chromosomes only one of them remains active and functional mixed to the chromatin while the other remains condensed and inactive.
In the same woman in some cell lineages the functional X chromosome is the one from the father and in other cell lineages the functional chromosome is the X fromthe mother characterizing a condition known as mosaicism (related to the X chromosome).
Under the microscope the inactive X chromosome is seen as a granule generally in the periphery of the nucleus. This granule is called the Barr body.
Image Diversity: Barr body
9. Besides the XY system are there other sex determination systems?
Some animals have a sex determination system different from the XY system.
The X0 system is the sex determination system of many insects; in this system the females are XX and the males have only one X chromosome (a conditioned represented by X0).
In birds, in some fishes and in lepidopterae (butterflies) insects the sex determination is made by the ZW system; in this system females are ZW and males are ZZ.
In another system, the haploid-diploid sex determination system, one of the sexes is represented by the fertilized diploid individual and the individual of the opposite sex is formed by parthenogenesis, being haploid (it occurs in bees and other insects).
10. What are X-linked traits?
X-linked traits are phenotypical traits conditioned by genes located in the nonhomologous (heterologous) portions of the X chromosome.
11. How many alleles of genes that condition X-linked traits do female and male individuals respectively present?
For each correspondent gene to an X-linked trait women present always two alleles since they have two X chromosomes. Men present only one allele of genes related to X-linked traits since they haveone X chromosome.
12. What is the clinical deficiency presented by hemophilic people? What is the genetic cause of that deficiency?
Hemophilia is a disease characterized by impaired blood clotting and the affected person is more prone to internal and external hemorrhages.
Patients with hemophilia A have alteration in the gene that codifies the factor VIII of blood clotting, a gene located in the nonhomologous portion of the X chromosome. Patients with hemophilia B present a defect of the gene that codifies the factor IX of clotting, a gene also located in the nonhomologous region of the X chromosome. Thus both diseases are X-linked diseases.
Image Diversity: hemophilia family tree
13. What are all possibilities of genotypes and phenotypes formed in the combination of alleles responsible for the production of factor VIII?
Considering the alleles Xh and X, where Xh represents the allele that conditions hemophilia A, in women the possible genotypes are XX, XXh and XhXh. In men the possible genotypes are XY and XhY. Concerning the phenotypes, factor VIII is produced in every individual with at least one nonaffected X chromosome. So the women XX and X Xh and the men XY are normal. Only women XhXh and men XhY have the disease.
14. Why is it rare to find hemophilic women?
There are more hemophilic men than hemophilic women because women need to have two X chromosomes affected to develop the disease while in men the disease manifests when the single X chromosome is affected.
15. Is it possible for any son of a couple formed by a hemophilic man (XhY) and a nonhemophilic noncarrier (XX) woman to be hemophilic?
If mothers are not affected by the disease and noncarriers of the gene (do not have an Xh allele) it is impossible for their sons to be hemophilic since the X chromosome of males always comes fromthe mother. Hemophilic sons are only possible when the mother is hemophilic (homozygous for the hemophilic gene, a very rare situation) or carriers of an affected X chromosome (XXh).
16. What is the clinical manifestation of the disease known as daltonism?
The X-linked daltonism is a disease in which the affected individual sees the red color as green or confounds these two colours.
17. What is the type of genetic inheritance of daltonism? Is daltonism more frequent in men or in women? What is the physiological explanation for the daltonism?
Daltonism is a recessive X-linked inheritance (gene situated in the nonhomologous portion of the X chromosome).
Daltonism is more frequent in men since in them only the single X chromosome needs to be affected for the disease to manifest. In women it is necessary for both X chromosomes to be affected for the disease to come out.
The disease appears due to a defect in the gene that codifies a retinal pigment sensitive to red.
18. Are sex-linked diseases associated only to genes of the X chromosome?
There are many X-linked diseases, like hemophilia A, hemophilia B and adrenoleukodystrophy, but known Y-linked diseases are few and very rare.
19. What are holandric genes?
Holandric genes are genes situated in the nonhomologous region of the Y chromosome. Holandric genes condition phenotypes that emerge only in men since individuals of the female sex do not present in their X chromosomes genes from the nonhomologous portion of the Y chromosome (existent only in men). A widely known holandric gene is the one that conditions hypertrichosis pinnae (hair in the ears), a phenotype inherited from fathers to sons through the Y chromosome.
20. What is sex-influenced dominance?
Sex-influenced dominance is the phenomenon in which the manifestation of a phenotype of a gene in heterozygosity depends on the sex of the individual. For example, hereditary baldness is a dominant phenotypical form if the individual is male and it is a recessive form if the individual is female.
Blood Types - Q&A Review
1. What are the main human blood group systems?
In humans the main blood group systems are the ABO system, the Rh system and the MN system.
2. Why is the determination of the blood types of the donor and of the recipient important in transfusions?
Red blood cells have different antigens in the outer surface of their plasma membrane; for example, the antigens A and B of the ABO system are glycoproteins of the membrane. If a donor has red blood cells with antigens not present in the red blood cells of the recipient (lacking of transfusion compatibility) the immune system of the recipient recognizes these molecules as actual antigens (i.e., foreign substances) and triggers a defense response producing specific antibodies against those antigens. The transfusedred blood cells then are destroyed by these antibodies and the recipient individual may even die.
Image Diversity: blood donation
3. What are the antigens and the respective antibodies of the ABO blood group system?
The ABO blood system includes the erythrocytic antigens A and B that can be attacked by the antibodies anti-A and anti-B.
The antigens A and B are agglutinogens and the antibodies anti-A and anti-B are agglutinins.
Blood Types - Image Diversity: ABO system
4. What are the blood types of the ABO blood system?
The blood types of the ABO blood system are the type A, the type B, the type AB and the type O.
5. What are the antigens and antibodies of each blood type of the ABO blood system?
Type A: antigen A, antibody anti-B. Type B: antigen B, antibody anti-A. Type AB: antigens A and B, does not produce antibody A neither antibody B. Type O: does not have antigen A neither antigen B, has antibodies anti-A and anti-B.
(Obviously antibodies are made by B lymphocytes not by red blood cells.)
6. What is the logic of the transfusional compatibility concerning the ABO blood group system?
The transfusional compatibility for the ABO system takes into account the antigens present in the red blood cells of the donor and the antibodies that the recipient can produce. Whenever the recipient is not able to produce antibodies against antigens of thered blood cells of the donor the transfusion is compatible.
So regarding ABO compatibility type A can donate to type A and to type AB. Type B can donate to type B and to type AB. Type AB can donate only to type AB. Type O can donate to all ABO types.
(Any transfusion must be studied, planned and supervised by doctors.)
7. What are universal donors and universal recipients concerning the ABO blood system?
Universals donors of the ABO blood type system are the individuals of the type O. Type O blood does not have antigen A neither antigen B in itsred blood cells and can be donated to individuals of any ABO type.
Universal recipients of the ABO blood type system are the individuals of the type AB. Type AB blood does not contain antibody anti-A neither antibody anti-B and people of this group can receive blood from any of the ABO types.
8. What is the type of genetic inheritance that determines the ABO blood group system? What are the relations of dominance among the involved alleles?
The inheritance of the ABO blood system is a multiple alleles inheritance. There are three involved alleles, IA, IB and i that combine in pairs to form the genotypes.
Concerning dominance, the allele i is recessive in relation to the alleles IA and IB. Between IA and IB however lack of dominance is established with the heterozygous (IAIB) manifesting distinct phenotype.
9. What are the genotypes and respective blood types of the ABO system?
Since the alleles are IA, IB and i the possible genotypes are IAIA (blood type A), IAIB (blood type AB), IBIB (blood type B) and ii (blood type O).
10. Is it possible to perform investigation of natural paternity, maternity or brotherhood and sisterhood using the ABO blood typing?
By using the ABO blood typing it is possible only to exclude paternity, maternity or brotherhood/sisterhood but it is not possible to conclude positively about these relationships.
For example, if an individual has type O blood, ii genotype, he or she cannot have biological parents of the type AB (IAIB genotype) since necessarily one of his/her alleles has come from the father and the other from the mother. Another example: a couple of individuals of the type O (ii) in their turn can only generate direct offspring of the type O blood, since they do not have alleles that condition antigen A neither antigen B.
11. Is ABO blood compatibility enough for the safety of blood transfusion?
Besides ABO blood compatibility the compatibility concerning the Rh blood system must also be checked. In addition it is of fundamental importance for the safety of blood transfusion performing tests to detect agents of main blood transmitted infectious diseases, like HIV (AIDS), hepatitis B and C, syphilis, Chagas disease, etc.
(Any transfusion must be studied, planned and supervised by doctors.)
12. What is the Rh factor?
RH factor is a protein of the red blood cell plasma membrane that behaves as antigen in blood transfusions triggering a humoral (antibody-based) immune response. Most people present the protein in theirred blood cells and are part of the Rh+ group. People that do not have the protein classify as Rh-.
The origin of the name Rh factor is related to the first researches that discovered this blood antigen was in rhesus monkeys (Macaca mulatta).
Image Diversity: rhesus monkeys
13. How are the antibodies against the Rh factor formed?
Anti-Rh antibodies are made by humoral immune response. When an Rh- individual makes contact with the Rh factor this is recognized as foreign (antigen), the primary immune response begins and small amounts of anti-Rh antibodies and memory B lymphocytes are made. In future contact with the antigen there will already be circulating antibodies and memory immune cells prepared to create an intense and effective attack against the Rh factor.
14. What is blood typing?
Blood typing is the determination, by means of tests, of the classification of a blood sample concerning blood group systems (specially theABO system and the Rh system).
Blood Types - Image Diversity: blood typing
15. How is the blood typing concerning the ABO system and the Rh usually done?
In the blood typing for the ABO system and the Rh system a blood sample is collected from the person and three small volumes of the sample are separated and dispersed on glass laminae (slides). On the first lamina serum containing anti-A antibody is dripped; on the second lamina serum containing anti-B antibody is dripped; on the third lamina serum with anti-RH antibody is dripped. If no agglutination reaction takes place in all of the laminae the blood is of type O- (universal donor); if agglutination occurs only in the first lamina the blood is type A-; and so on.
There are other methods of blood typing. Blood typing must be performed by qualified technicians.
16. What are the inheritance and dominance patterns of the Rh blood system?
The inheritance pattern of the Rh blood system is autosomal dominant, i.e., the heterozygous manifests as Rh+. The dominance is complete (R is dominant over r). The possible genotypes are RR, Rr (both Rh+) and rr (Rh-).
Curiosity: the Rh factor is codified by a gene containing 2790 DNA nucleotides situated in the human chromosome 1.
17. What is the logic of the transfusional compatibility concerning the Rh blood group system?
An Rh+ donor can only donate blood to an Rh+ recipient. A person that lacks the Rh factor (Rh-) can donate to individuals of the Rh+ and Rh- groups.
18. What is the Rh typing of the mother and of the fetus in the hemolytic disease of the newborn?
In the hemolytic disease of the newborn the mother is Rh- and the fetus Rh+. In this disease antibodies produced by the mother attack the fetal red blood cells.
The hemolytic disease of the new born is also known as erythroblastosis fetalis.
19. How does the immune process that causes the hemolytic disease of the newborn take place?
In the hemolytic disease of the newborn the mother has Rh- blood. This mother when generating her first Rh+ child makes contact, possibly during delivery, with Rh+ red blood cells of the child and her immune system triggers the primary immune response against the Rh factor. In the next gestation in which the fetus is Rh+ the mother will already have much more anti-Rh antibodies in her circulation; these antibodies cross the placental barrier and gain the fetal circulation causing fetal hemolysis (destruction of thered blood cells of the fetus).
Image Diversity: hemolysis
20. How can the hemolytic disease of the newborn be prevented?
Erythroblastosis fetalis can be prevented if in the first delivery of a Rh+ child from a Rh- mother serum containing anti-Rh antibodies is given to the mother in the first 72 hours (after the delivery). Therefore the administered anti-Rh antibodies destroy the fetal red blood cells that entered the mother’s circulation before the triggering of her primary immune response.
21. What is the MN blood system? What is the pattern of genetic inheritance of the MN blood system?
The MN blood system is a third (in addition to the ABO and the Rh) system of blood antigens also related to proteins of the red blood cell plasma membrane.
The inheritance pattern of the MN blood system is autosomal with codominance, a type of lack of dominance in which the heterozygous manifests a phenotype totally distinct from the homozygous. The possible phenotypical forms are three blood types: type M blood, type N blood and type MN blood.
A Q&A Review of Genetic Diseases
1. What is karyotype?
The name karyotype is given to the set of chromosomes of an individual, usually when visualized and identified under the microscope. The visualization generally is made with the cells in the initial phases of cell division for the chromosomes to be seen already replicated and condensed.
Image Diversity: human chromosomes
2. Which type of genetic disease can be identified from the visual analysis of the number of chromosomes present in a karyotype?
The counting and identification of chromosomes in the karyotype of an individual can diagnose the aneuploidies, diseases caused by alteration inthe number of chromosomes in relation to the normal number of the species.
3. Why in the preparation of a karyotype analysis is the use of a substance like colchicine interesting?
Colchicine is a substance that disallows the formation of microtubules and thus of the spindle fibers in cell division. Under the action of this drug the cells interrupt division at metaphase and the anaphase does not occur. Therefore the use of colchicine in the study of karyotypes is interesting because chromosomes will be seen replicated and condensed.
4. What is the karyotype found in Down syndrome?
Down syndrome is an aneuploidy, i.e., a numeric alteration of chromosomes within the cells compared to the normal number of chromosomes of the species. Affected individuals have in their cells an additional chromosome 21 instead of only one pair. For this reason the condition is also called trisomy 21. The affected person has karyotype with 47 chromosomes: 45 + XY or 45 + XX.
Image Diversity: trisomy 21 karyotype
5. What is aneuploidy? What are the conditions caused by the aneuploidies?
Aneuploidy is an abnormal number of chromosomes in the cells of an individual.
The main aneuploidies of the human species and their respective conditions are: the nullisomies (absence of any chromosome pair of the species, often incompatible with life); the monosomies (absence of a chromosome from a pair, for example, Turner’s syndrome, 44 + X); the trisomies (an extra chromosome, for example, the triple X syndrome, 44 + XXX, or the Edwards syndrome, trisomy 18, 45 + XY or 45 + XX).
6. In general what is the cause of the aneuploidies?
Generally the aneuploidies are caused by impaired assortment of chromosomes during meiosis. For example, when the homologous chromosomes of the pair 21 do not separate gametes with two chromosomes 21 and gametes without chromosomes 21 form. If a gamete with two chromosomes 21 fecundates a normal gamete of the opposite sex the zygote will present trisomy (three chromosomes 21). If a gamete without chromosomes 21 fecundates a normal gamete of the opposite sex there will be a zygote with monosomy (with only one chromosome 21).
The defects in the separation of chromosomes during cell division are called chromosomal nondisjunctions. During meiosis nondisjunctions may occur in theanaphase I (nondisjunction of homologous) as well in anaphase II (nondisjunction of sister chromatids).
Image Diversity: chromosomal nondisjunctions
7. Do all genetic diseases result from alteration in the number of chromosomes of the cells?
Besides aneuploidies there are other genetic diseases, other chromosomal abnormalities and also the genetic mutations.
8. How are genetic diseases classified?
Genetic diseases classify into chromosomal abnormalities and genetic mutations.
Among chromosomal abnormalities there are the aneuploidies, diseases caused by alterations of the normal (euploidy) number of chromosomes of the species. An example of aneuploidy is Down syndrome, or trisomy 21, in which there are three chromosomes 21 instead of the normal pair. In the group of chromosomal abnormalities there are also the deletions (absence of part of a chromosome), the inversions (in which a chromosome breaks and its pieces reconnect in inverse manner) and the translocations (pieces of a chromosome that exchange positions).
In the genetic mutation group there are the deletions (one or more DNA nucleotide absent), the substitutions and the insertions.
Image Diversity: chromosomal deletions chromosomal inversions chromosomal translocations
9. What are genetic mutations?
Genetic mutations are alterations of the genetic material (compared to the normal condition of the species) involving modifications in the normal nucleotide sequence of a gene but without structural or numeric chromosomal changes.
These modifications may be deletions (loss of nucleotides), substitutions (exchange of nucleotides by other different nucleotides) or insertions (placement of additional nucleotides in the DNA molecule).
Image Diversity: genetic mutations
10. Does every gene mutation cause alteration in the protein the gene normally codifies?
Not every gene mutation causes alteration in the composition of the protein the gene codifies. Since the genetic code is degenerated, i.e., there are amino acids codified by more than one different DNA nucleotide triplet, if by chance the mutation substitutes one or more nucleotides of a codifier triplet and the newly formed triplet still codifies the same amino acid codified by the original triplet there will be no modification in the protein made from the gene.
11. How do genetic mutations influence biological diversity?
Too extensive or too frequent genetic mutations generally are deleterious for individuals and species. These mutations often cause important phenotypical changes or defects incompatible with the survival of the body and the continuity of the species.
However small genetic mutations that do not cause the appearing of lethal changes are continuously accumulated in the genetic patrimony of the species. These mutations gradually add to each other giving birth to small phenotypical changes in individuals. These small changes are exposed to the selective criticism of the environment (natural selection) and the more favorable for survival and reproduction are preserved (the remaider are eliminated as their carriers have difficulty in surviving and reproducing). In this manner the combined processes of accumulation of small mutations and of natural selection incorporate new features in the species and they may even lead to speciation (formation of new species) and promotion of biological diversity.
(Obviously only genetic mutations transmitted by cells that originate new individuals, in sexual or asexual reproduction, have evolutionary effect.)
12. What are mutagenic agents?
Mutagenic agents, or mutagens, are physical, chemical or biological factors that can cause alteration in DNA molecules.
Examples of well-known or believed to be mutagenic agents are: X, alpha, beta and gamma rays, ultraviolet radiation, nitrous acid, many dyes, some sweeteners, some herbicides, many substances of tobacco, some viruses, like HPV, etc. Small DNA fragments known as transposons can also act as mutagens when incorporated into other DNA molecules.
13. How are mutagenic agents related to cancer incidence in a population? Is cancer a disease transmitted to the individual offspring?
The exposition of a population to mutagenic agents (for example, the people living in the surrounds of the Chernobyl nuclear power plant and exposed to the radiation from the nuclear accident in 1986) increases the cancer incidence in that population. This occurs because the mutagenic agents increase the rate of mutation and the probability of mutant cells to proliferate in pathological manner (cancer).
Cancer itself is not a hereditarily transmissible disease. Genetic predispositions for the development of cancer, however, can be inherited.
14. How do the repairing enzymes of the genetic system act?
There are enzymes within the cells that detect errors or alterations in DNA molecules and begin a repair of those errors. First, enzymes known as restriction endonucleases, specialized in cutting DNA molecules (also used in genetic engineering), cut the affected piece of DNA. Then polymerase enzymes build correct sequences of nucleotides correspondent to the affected piece taking as template the DNA chain complementary to the affected chain. Finally the new correct sequence is bound in the DNA under repair by specific enzymes.
Image Diversity: DNA repairing system
15. What are some diseases or genetic abnormalities caused by recessive genes?
Examples of recessive genetic diseases are: cystic fibrosis, albinism, phenylketonuria, galactosemia, Tay-Sachs disease.
16. What are some diseases or genetic abnormalities caused by dominant genes? Why are severe dominant genetic diseases rarer than recessive ones?
Examples of dominant genetic diseases are: Huntington's disease (or Huntington’s chorea), neurofibromatosis, hypercholesterolemia, polycystic kidney disease.
Severe and early autosomal dominant diseases are rarer than recessive autosomal diseases because in this last group the affected allele may be hidden in the heterozygous individuals and transmitted to the offspring until undergoing homozygosity (actual manifestation of the disease). In severe dominant diseases the heterozygous manifests the condition and often dies without having offspring. (Some genetic diseases are of later manifestation, like Huntington disease; in these cases the incidence is higher because many individuals have children before knowing that they are carriers of the dominant gene).
17. What is consanguineal marriage? Why is the appearing of genetic disease more probable in the offspring of a consanguineal marriage?
Consanguineal marriage is the marriage between relatives, i.e., people having common near ancestors.
The consanguineal marriage increases the probability of recessive genetic disease in the offspring since it is common for people from the same genetic lineage to be heterozygous carriers of alleles that condition recessive genetic diseases.
18. How is the early diagnosis of genetic diseases usually done?
Genetic disease may be diagnosed in the prenatal period by karyotype analysis, in case of aneuploidies, or by DNA analysis, in case of other diseases.
The test is performed by removal of material containing cells of the embryo by amniocentesis (extraction of amniotic fluid) or cordocentesis (puncture of the umbilical cord) or even by chorionic villus biopsy (that can be done earlier in gestation).
Ultrasonography is a diagnostic procedure for some genetic diseases that produce morphological variations during the embryonic development. The study of genetic family trees is also an important auxiliary method in the early diagnosis of many genetic diseases.
Review of the Hardy-Weinberg Principle
1. What is allele frequency?
Allele frequency is the percentage of appearances of an allele in the genotypes of a given population (compared to the other alleles of the studied gene).
For example, in the ABO blood system there are three alleles (IA, IB and i). Considering a group of three persons, one with genotype IAi, other IAIB and other ii, the frequency of the allele IA in this “population” is 2/6, the frequency of the allele IB is 1/6 and the frequency of the allele i is 3/6.
2. What is genetic equilibrium?
Genetic equilibrium is the result of the Hardy-Weinberg law, a principle that affirms that under specific conditions the frequencies of thealleles of a gene in a given population remain constant.
(The Hardy-Weinberg principle is not valid in the following conditions: for populations too small, in the occurrence of noncasual (driven) crossings, for populations with many infertile members and in case of action of evolutionary factors, like natural selection, mutations and migrations.)
Hardy-Weinberg - Image Diversity: Hardy-Weinberg rule
3. What is the mathematical expression of the genetic equilibrium for genes with two alleles? Is this statistical distribution the same as the statistical distribution of the respective phenotypes?
Considering p the frequency of one of the alleles and q the frequency of the other allele of a given gene in a population, in this population individuals produce p gametes with the first allele for each q gamete containing the second allele. Therefore the probabilities of formation of homozygous genotype for the first allele is p2, of homozygous genotype for the second allele is q2 and of the heterozygous genotype is p.q + q.p, i.e., 2p.q.
Since the sum of those probabilities necessarily is 1, the resulting mathematical expression is: p.p + 2p.q + q.q = 1.
In general the number of genotypical forms is not identical to the number of phenotypical forms since there are dominance and other interactions between genes that affect the manifestation of the phenotype.
4. An hypothesis for the extinction of the dinosaurs is that the earth had been hit by a gigantic meteor that caused the death of those big reptiles. In that case the entiregenetic pool of those animals has been destroyed, invalidating the Hardy-Weinberg equilibrium. In Genetics what is this type of gene frequency change called?
The phenomenon in which a large number of genes is destroyed or introduced in a population is called genetic drift.
When a genetic drift occurs the Hardy Weinberg principle is not applicable.
Hardy Weinberg - Image Diversity: genetic drift
5. What are the penetrance and the expressivity of a gene?
Individuals that carry a same genotype do not always manifest in an identical manner the correspondent phenotype. These manifestations may differ in intensity, from one individual to another, or even the phenotype may not manifest in some percentage of carriers.
Gene penetrance is the percentage of phenotypical manifestation of a gene in a given population of carrier individuals (same genotype). Gene expressivity is the degree (intensity) of the phenotypical manifestation of a gene in each individual or group of individuals that carry the gene (same genotype). The gene penetrance and the gene expressiveness may be influenced by the environment.
6. Why is a balanced frequency of different alleles of a gene in a population more useful for the survival of that population facing environmental changes?
For a trait conditioned by two alleles, for example, A and a, a balanced frequency between the alleles A and b is more advantageous for survival. For example, in an environmental situation in which the aa homozygous phenotype becomes incompatible with life the presence of a good number of individuals AA and Aa will result in better survival chance for the species. Another example: an environmental situation in which the dominant phenotype becomes incompatible with life; in this case the existence of heterozygous and recessive homozygous individuals in enough number may be fundamental for the survival of the species.
Learn the Fundamentals of Biotechnology
1. What is biotechnology?
Biotechnology is the application of biological knowledge to obtain new techniques, materials and compounds of pharmaceutical, medical, agrarian, industrial and scientific use, i.e., of practical use.
The pioneer fields of biotechnology were agriculture and the food industry but nowadays many other practical fields use its techniques.
2. What is genetic engineering?
Genetic engineering is the use of genetic knowledge to artificially manipulate genes: It is one of the fields of biotechnology.
3. At the present level of the biotechnology what are the main techniques of genetic engineering?
The main techniques of genetic engineering today are: the recombinant DNA technology (also called genetic engineering itself) in which pieces of genes from an organism are inserted into the genetic material of another organism producing recombinant beings; the nucleus transplantation technology, popularly known as “cloning”, in which a nucleus of a cell is grafted into a enucleated egg cell of the same species to create a genetic copy of the donor (of the nucleus) individual; the technology of DNA amplification, or PCR (polymerase chain reaction), that allows millions replications of chosen fragments of a DNA molecule.
The recombinant DNA technology is used to create transgenic organisms, like mutant insulin-producing bacteria. The nucleus transplantation technology is in its initial development but it is the basis, for example, of the creation of “Dolly” the sheep. PCR has numerous practical uses, as in medical tests to detect microorganisms present in blood and tissues, DNA fingerprint and obtainment of DNA samples for research.
4. What are restriction enzymes? How do these enzymes participate in the recombinant DNA technology?
Restriction enzymes, or restriction endonucleases, are enzymes specialized in the cutting of DNA fragments each acting upon specific sites of the DNA molecule.Restriction enzymes are used in the recombinant DNA technology to obtain with precision pieces of DNA molecules to be later inserted into other DNA molecules cut by the same enzymes.
Image Diversity: recombinant DNA technology restriction enzymes
5. What are DNA ligases? How do these enzymes participate in the recombinant DNA technology?
DNA ligases are enzymes specialized in tying the complementary DNA chains that form the DNA double helix. These enzymes are used in therecombinant DNA technology to insert pieces of DNA cut by restriction enzymes into other DNA molecules submitted to the action of the same endonucleases.
Image Diversity: DNA ligases
6. What are plasmids?
Plasmids are circular DNA molecules present in the genetic material of some bacteria. They may contain genes responsible for bacterial resistance to some antibiotics and for proteins that cause virulence (pathogenic hostility).
Image Diversity: plasmid
7. How is genetic engineering used to create bacteria capable of producing human insulin?
In the production of human insulin by bacteria the human insulin gene is incorporated into the genetic material of these microorganisms. The mutant bacteria multiply forming lineages of insulin-producing bacteria.
In bacteria there are circular strands of DNA called plasmids, minichromosomes which act as an accessory to the main DNA. To create a mutant bacteria capable of producing insulin a plasmid is submitted to the action ofrestriction enzymes (restriction endonucleases) specialized in cutting DNA fragments. The once circular plasmid is open by the restriction enzyme. The same enzyme is used to cut a human DNA molecule containing the insulin gene. The piece of human DNA containing the insulin gene then has its extremities bound to the plasmid with the help of DNA ligases. The recombinant plasmid containing the human insulin gene is then inserted into the bacteria.
Another human hormone already produced by recombinant bacteria is GH (somatotropin, or growth hormone).
The insertion of DNA molecules into cells of an individual is also the method of the gene therapy, a promising treatment for genetic diseases. In gene therapy cells from an organism deficient in the production of a given protein receive (by means of vectors, e.g., virus) pieces of DNA containing the protein gene and they then begin to synthesize the protein.
8. What is cloning?
Cloning is the making of an organism genetically identical to another by means of genetic engineering.
The basis of cloning is the nucleus transplantation technology. A nucleus from a cell is extracted, generally from an embryonic (not differentiated) cell and this nucleus is inserted into a previously enucleated reproductive cell (in general an egg cell); the egg is then implanted in the organ where the embryonic development will take place. If embryonic development occurs the new organism will have identical genetic patrimony to the organism owner of the cell whose nucleus was used in the transplantation.
Image Diversity: genetic cloning Dolly the sheep
9. What is PCR? How does PCR works?
PCR, polymerase chain reaction, is a method to synthesize many copies of specific regions of a DNA molecule known as target-regions. Its inventor, Kary Mullis, won the Nobel prize for Chemistry in 1993.
First, the DNA to be tested is heated to cause the double helix to rupture and the polynucleotide chains to be exposed. Then small synthetic sequences of DNA known as primers and containing nucleotide sequences similar to the sequences of the extremities of the region to be studied (for example, a region containing a known gene exclusive of a given organism) are added. The primers paired with the original DNA in the extremities of the gene to be amplified. Enzymes known as polymerases, that catalyze DNA replication, and nucleotide supply are added. The primers then are completed and the chosen region is replicated. In the presence of more primers and more nucleotides millions of copies of that specific region are generated. (PCR is very sensitive even using a minimal amount of DNA).
Image Diversity: polymerase chain reaction
10. What is the fact of Molecular Biology on which DNA fingerprint is based?
DNA fingerprint, the method of individual identification using DNA, is based on the fact that the DNA of every individual (with exception of identical twins and individual clones) contains nucleotide sequences exclusive to each individual.
Although normal individuals of the same species have the same genes in their chromosomes, each individual has different alleles and even in the inactive portions of the chromosomes (heterochromatin) there are differences in nucleotide sequences among individuals.
Image Diversity: DNA fingerprint
11. Why are the recombinant DNA technology and the nucleus transplantation technology still dangerous?
The recombinant DNA technology and the nucleus transplantation technology (cloning) are extremely dangerous since they are able to modify, in a very short time, the ecological balance that evolution has taken millions of years to create on the planet. During the evolutionary process, under the slow and gradual action of mutations, genetic recombinations and of natural selection species emerged and were modified and genetic patrimonies were formed. Withgenetic engineering however humans can mix and modify genes, making changes of unpredictable long term consequences, risking creating new plant or animal diseases, new types of cancers and new disease outbreaks. It is a field as potentially dangerous as the manipulation of nuclear energy.
12. What is the main moral problem about the cloning of human individuals?
Besides biological perils, a very serious moral problem involves the nucleus transplantation technology concerning humans: an individual right of a human being is offended when a man or woman is made as a copy of another.
Since it is impossible to first ask if the person to be generated wants or not to be a genetic copy of another person, certainly the most important human right is being offended, one's individual freedom, when a human being is obliged to be a genetic copy of another. It is indeed a danger to democracy, whose most basic principle must be nonviolation of individual freedom.
ليست هناك تعليقات:
إرسال تعليق