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The rules of inheritance had already been established before the mechanisms on the cellular and molecular level were comprehended. Memorize the following genetic fundamentals very well:
- Allele: a unit of inheritance resulting in a specific trait (original gene (normal allele or “wild type”) or mutated gene)
- Genetic locus: location of a gene in the genome
- Diploid set of chromosomes: two sets of genes of homologue chromosomes
- Genotype: complete genetic information of an organism (entire combination of alleles)
- Phenotype: A genetic trait can but does not necessarily have to be expressed in its appearance. This expression is called phenotype.
- Homozygous: Both homologue chromosomes have the same alleles.
- Heterozygous: Homologue chromosomes have different alleles.
- Hemizygosity: Only one copy of a gene is present despite the diploid set of chromosomes.
- Polymorphism/multiple alleles: More than two alleles of a gene are present in a population.
Types of Inheritance: Dominant, Recessive, and Codominant
If an allele is dominant, it is more expressive than the other allele. A recessive allele, on the other hand, reverts to the phenotype in its effect. Recessive allele only can manifest in the phenotype in a homozygous genotype. Codominance means that both alleles are expressed in the phenotype, i.e. blood type AB.
Traits in the phenotype can also be mixed, which is referred to as intermediate inheritance, i.e. height. Expressivity refers to the degree of expression of a trait. Penetrance, on the other hand, refers to the extent in which a trait is present (measured by the proportion of gene carriers).
Conductors are genetic carriers that carry the trait not in the phenotype but rather recessively in the genotype. Therefore, a conductor can pass on recessive alleles to their descendants without displaying the traits themselves (i.e. red hair). Should a gene control several traits, it is referred to as pleiotropy. Polygenic traits, on the other hand, are controlled by several genes.
The environmental influence: Phenocopy
The genetic analysis of the origin of disease becomes difficult if environmental factors are involved, the phenocopies.
Phenocopies can simulate a genetic cause at first.
Iodine deficiency, for instance, can phenotypically be mistaken for cretinism (genetically determined dwarfism). Cretinism is a genetic mutation of the TSH or TRH hormone. In cases of iodine deficiency, insufficient thyroid hormones are produced. Both cases lead to hypothyroidism.
The punnett square
The punnett square, also referred to as combination square, was developed by the British geneticist R. Punnett in order to depict the frequency of genotypes in inheritance.
- Capital letters: dominant allele
- Both parents are in bold print (example: one part heterozygous Rr and homozygous RR).
- Lower case letters: recessive alleles
- The dominant allele is named first.
Another example can be found in the third Mendel’s rule.
In our article concerning human genetics, you can read everything regarding pedigree analysis, important diseases as well as many interpretation examples.
The „father of genetics“ Gregor Mendel (1822 – 1884), an Augustine monk, performed cross-breeding experiments with peas and beans from his monastery’s garden and deduced from them the laws of inheritance named after him. In 1865, he presented them in Bruenn for the first time where his discoveries were initially disregarded by experts. Later, Sutton and Boveri postulated the chromosome theory which built on Mendel’s discoveries.
Mendel assumed hereditary factors, which can be passed on by the parental generation to the filial generation. His derived laws describe the inheritance of uncoupled autosomal genes according to statistical laws.
First Mendel’s law: The principle of uniformity
All descendants (F1 generation) of homozygote parents (P generation) are uniform.
AA × aa = 100 % Aa
If both homozygous parents carry different alleles of a trait, the F1 generation will be uniformly heterozygous. This rule applies independently from the hereditary type (dominant/recessive, codominant or intermediate).
- Dominant-recessive inheritance: The dominant allele always dominates in the phenotype (i.e. long stems).
- Intermediate inheritance: Both alleles influence one another (i.e. flower colors red and white result in pink in the F1 generation).
- Codominant inheritance: Both traits are expressed in the phenotype independently of one another (i.e. blood types AA and BB all have F1 AB).
Second Mendel’s law: The principle of segregation
If the heterozygous F1 hybrid generation is crossbred, the F2 generation is split phenotypically according to a certain number ratio (1 : 2 : 1 or 1 : 3).
Aa × Aa = 25 % aa + 50 % Aa + 25 % AA
- Dominant-recessive inheritance: The recessive inheritance trait reappears in 25 % of descendants. The rest is homozygous for the dominant gene or heterozygous with the appearance of the dominant trait.
- Intermediate inheritance: Both original traits of the P generation are homozygous again in 25 % of descendants.
Third Mendel’s rule: The principle of independent assortment
So far, Mendel had examined the characteristics of the inheritance of one single trait. After that, he analysed plants that had two different traits. Here, he also analysed that the F1 generation was identical genotypically as well as phenotypically. If he crossed the F1 hybrids anew, however, new trait combinations appeared in the F2 generation.
If individuals whose genetic makeup differs in several traits are crossed, the individual traits are inherited independently of each other according to Mendel rules one and two.
Self-pollination results in 4 × 4 = 16 allele combinations.
Exception: Neighbouring genes are inherited together as a coupled group. (Therefore, Mendel’s achievements were recognized only posthumously because his discoveries could not be completely verified due to these limitations.)
The following is only applicable to a certain extent as well: The coupled inheritance of allele combinations is interrupted by crossing-over. The crossing-over frequency increases in proportion to the distance of two genes in a chromosome.
The Hardy-Weinberg law
In studies regarding population genetics, it is not the individual that is the focus but rather larger groups of individuals that reproduce together. This population provides a common gene pool. The gene pool contains several alleles of one gene and the relative proportions of these alleles are called gene frequency. Gene flow is created if individuals migrate into or away from the population.
In 1908, Hardy and Weinberg found (independently of one another):
The frequencies of the alleles and the genotypes remain constant over generations within a population if the genetic recombination takes place according to Mendel’s rules without any export out of or import of genes into the existing gene pool. Hence, a mathematical model can be derived via the probability test: the Hardy-Weinberg equation.
The Hardy-Weinberg equation
With the aid of the Hardy-Weinberg equation, population geneticists calculate what percentage of a certain disease the gene carries.
If gene A and gene a are distributed in a population which is constant, the following applies:
p + q = 1 or 100 %
Gene frequency according to the Hardy-Weinberg equation
The frequencies result from the Punnett square.
- Genotype AA: frequency p2
- Genotypes Aa, aA: frequency 2pq
- Genotype aa: frequency q2
Reference: T. Wenisch (2013): mediscript Kurzlehrbuch Biologie, S. 94, Tab. 2.4. Elsevier Verlag.
The Hardy-Weinberg equation: p2 + 2pq + q2 = 1
The Hardy-Weinberg applies if…
- …a purely coincidental pairing of individuals in the population occurs.
- …there are no selection effects (favouring certain genotypes).
- …there is no gene flow and/or mutation in the gene pool.
- …the population is large enough that the probabilities are equal to the frequencies.
These prerequisites only apply to a shorter observation period. Changes in the gene pool always occur over a longer period of time.
Question: In a population, the dominant allele is present with a frequency of 60 % in the gene pool. What does the distribution of the possible genotypes within the population look like?
p = 60 %, q = 40 %, because q + p = 100 %
(0,6)2 + 2 × (0,6 × 0,4) + (0,4)2 = 1
0,36 + 0,48 + 0,16 = 1
p2 = 36 %, pq = 48 %, q2 = 16
Answer: 36 % are AA, 48 % are Aa, 16 % are aa.
Selection and coincidence
Over longer periods of time, the gene pool of a population always changes: Genes are imported or change due to coincidental new mutations. Natural selection favours individuals with a genetic composition that secures the survival and reproduction chances or even increases them. Their genes will occupy a growing share of the gene pool over a longer period of time.
If the genes that offer survival advantages are dominant, they spread rapidly. On the other hand, dominant genes that are disadvantageous for the individual, disappear quickly. Recessive gene remain longer in a population.
Sickle cell anemia: Selective advantages through gene defects
Sickle cell anemia represents an example for a regionally frequent gene defect, which offers its carriers a selective advantage. Sickle cell anemia, a hemolytic anemia, is especially prevalent among black Africans. Heterozygous carriers, who carry the HbS gene, have a higher resistance to malaria than non-carriers. Thus, through their selective advantages, the conductors in malaria-endemic regions receive a high share of the HbS gene in the gene pool of the population.
Tay-Sachs disease: The founder effect
If a smaller group isolates itself from a population, splits off and reproduces, a genetic drift is more than likely. If a genetic drift develops in a new colony, it is referred to as founder effect. Tay-Sachs disease is an example for the founder effect: This disease is especially common among Ashkenazic Jews in the USA.
You have already come across the term polymorphism under genetic fundamentals. Genetic polymorphisms are categorized in the “normal“ range. Various alleles mutate incidentally and are not to be considered pathological. If these varying genotypes occur frequently, however, they are referred to as polymorphisms.
Proteins and enzymes are not functional in all variables but rather only in a certain configuration. An enzyme/protein polymorphism exists if the polymorphism is of consequence in the genome as well, meaning the gene products can thus be differentiated, i.e. in an enzyme.
The combination possibilities of the variables mean biochemical individuality for every human being.
Every human being can be identified through the “genetic finger print.”
One exception is identical twins: They have an identical genome.
In uniparental disomy, both chromosomes of a homologue chromosome pair come from one parent. This leads to a disruption of genomic imprinting. One differentiates between two forms:
- Paternal uniparental disomy: The maternal chromosome and its genes are missing.
- Maternal uniparental disomy: The paternal chromosome and its genes are missing.
Failure of genetic expression or overexpression of genomic imprinting can lead to diseases, i.e. Prader-Willi syndrome or Angelman syndrome.
The disruption of imprinting caused by uniparental disomy is not passed on to the next generation. The expression of genetic information takes place anew and there is no increased risk of recurrence in families.
Popular Exam Questions Regarding Biology for Physicians: Genetics
The answers can be found below the references.
1. In a population, every fiftieth individual is heterozygous for an allele resulting in phenylketonuria in homozygotes. How high is the frequency of this disease in this population?
- 1 : 100
- 1 : 2,500
- 1 : 5,000
- 1 : 10,000
- 1 : 100,000
2. In families with two children, both parents are heterozygous for the same gene. This gene causes an anomaly in homozygotes. How high is the expected share of families in which both children have this anomaly?
- 1 / 25
- 1 / 16
- 1 / 8
- 1 / 4
- 1 / 2
3. Which disease is caused by uniparental disomy, a disruption of genomic imprinting?
- Prader-Willi syndrome
- Down syndrome
- Arnold-Chiari malformation
- DiGeorge syndrome
- Duchenne muscular dystrophy
T. Wenisch (2013): mediscript Kurzlehrbuch Biologie. Elsevier Verlag.
G. Poeggel (2009): Kurzlehrbuch Biologie. Thieme Verlag.
Rechenbeispiel Hardy-Weinberg-Gleichung via Ernst Klett Verlag
Correct Answers: 1D, 2B, 3A