LON-CAPA Lecture 24: Mendelian Inheritance (part II)

Lecture 24: Mendelian Inheritance (part II)

How did he explain all of this?
Mendel's First Law: The Law of Segregation
1. Each plant has two determinants (alleles) for each trait.
2. Each plant transmits in a random manner only one of its determinants to each of its progeny plants. The determinants segregate from each other and are transmited separately.
3. For some determinants (alleles), the presence of one copy (heterozygous) is enough to express the trait (dominant). For other determinants, two copies (homozygous) must be present for the trait to be expressed (recessive).

Look at this in more detail
1. Each individual has two copies of a gene
2. Each indivdiual donates one copy of a gene to each progeny in a random manner
3. Example
  - two alleles: A and a
  - AA x AA gives all AA
  - AA x aa gives all Aa
  - AA x Aa gives 1/2 AA and 1/2 Aa
  - Aa x aa gives 1/2 Aa and 1/2 aa
  - Aa x Aa gives 1/4 AA, 1/2 Aa and 1/4 aa
4. If trait is recessive
  - aa shows the trait
  - AA, Aa do not show the trait
  - the progeny of a mating between two heterozygotes (Aa x Aa) results in 3/4 to 1/4 ratio of dominant to recessive
  - examples: alopecia, methemoglobinemia, sugary in maize
5. If a trait is dominant
  - AA and Aa show the trait, need only one copy of the associated allele
  - aa does not show the trait
  - the progeny of a mating between two heterozygotes (Aa x Aa) results in 3/4 to 1/4 ratio of dominant to recessive
  - the progeny of a mating between a heterozygote and a homozygote recessive (Aa x aa) results in a 1 : 1 ratio of dominant to recessive
  - examples: Familial HyperCholesterolemia, variegate porphyria, Yellow endosperm in maize

The testcross is a more direct method of testing the genotype of an organism with a dominant trait
1. An organism with the dominant trait can be either homozgyous (AA) or heterozygous (Aa)
2. Crossing the organism with one with the recessive trait (aa) allows for
  - a homozygous dominant (AA) to produce all heterozygous (Aa) and dominant progeny
  - a heterozygous dominant (Aa) to show equal segregation for the dominant and recessive traits
  - AA X aa gives all Aa
  - Aa X aa gives 1/2 Aa and 1/2 aa
  - looking for a 1:1 ratio or a variance from that ratio requires fewer progeny than looking for a 3:1 ratio

Does this work with two traits?
Mendel's Second Law: The Law of Independent Assortment
1. The analysis of two, different genes in the same mating
2. Both follow the rules for single genes in an independent manner
3. Usually, the inheritance patterns are independent unless the genes for the traits are located on the same chromosome on the same arm
4. the F1 hybrid shows only the two dominant traits even though it is heterozygous at each gene
5. the F2 progeny show four phenotypic ratios in a 9 : 3 : 3 : 1 ratio which is merely the product of two 3 : 1 ratios
6. the F2 progeny have a genotypic ratio of 1:2:2:4 : 1:2 : 1:2 : 1 and this can be demonstrated by allowing self-mating and examining the segregation patterns in the F3

Correlates with Meiosis
1. Mendel was not aware of chromosomes, mitosis or meiosis - that all came later.
2. However, the segregation of alleles has a perfect parallel in the separation of homologous chromosomes at meiosis anaphase I.
3. And the independent assortment of different traits has a perfect parallel in the independent alignment of non-homologous chromosomes in metaphase I.
4. Thus, the behavior of chromosomes fits perfectly with the behavior of chromosomes and suggests that genes are on chromosomes. This suggestion was made in the early 1900's by Sutton.
5. The final proof that genes are located on chromosomes came from the observation that a particular genetic trait was absolutely correlated with a particular chromosome.

Extensions to Mendelian Inheritance

Phenotypes and Genotypes
1. The determination of a phenotype can be made at multiple levels:
  - at"arm's length" - tall, short, color, etc.
  - at the surface - rough, smooth, scaly, etc.
  - microscopic - low to high magnification
  - biochemical
    - gene product - enzyme activity, protein structure, amino acid sequence, etc.
    - gene - DNA sequence
2. The phenotype depends on the organism's requirement for the quantity and quality of the gene product.
3. It is possible to measure the phenotype at different levels and demonstrate a different inheritance pattern at each level of phenotype measurement
  - Phenylketonuria (PKU) can be measured at"arm's length" by measuring IQ.
    In this case, the trait of mental retardation is inherited as a recessive.
  - PKU can also be measured at one biochemical level of enzyme activity.
    In this case, the trait of enzyme activity is inherited as an incomplete dominant (heterozygote phenotype is intermediate between the two homozygote phenotypes).
  - Another measurement at the biochemical level is the concentration and amino acid sequence of enzyme molecules.
    In this case, the trait of molecule type is inherited as a co-dominant (both phenotypes are expressed in the heterozygote).
  - A similar analysis can be made for the snapdragon color example shown in Fig. 10.11 in the text. In this case, one could categorize snapdragons as white or colored and score colored as a dominant trait.
4. Thus, the words dominant and recessive should not be applied to alleles or genes but are applied to inheritance patterns of measured phentoypes.

Aspects of Alleles
1. Depending on the function of a gene product, it may be possible to measure a phenotype in more than one place at the same level. A trait that has multiple, measurable effects is said to be pleiotropic.
2. New alleles are produced by mutation
  - mutation creates a stable, heritable change in a gene form = a new allele
  - in general, a specific allele of a gene is called the wild-type
    in the wild, it would be more reasonable to refer to the most prevalent allele
  - alleles are named using letters or short words that have some relation to the gene function or phenotype - HbS globin mutation is associated with sickle-cell anemia
  - often alleles are capitalized if they are associated with a dominant inheritance pattern
3. most genes have multiple alleles but the alleles may not occur with equal frequency in the population
  - the ABO blood group system has three (3) major alleles I^A, I^B, and i
  - the Rh blood group (Rhesus) system has 8 major alleles although Rh-incompatibility is seen as a two allele system
  - there are literally hundreds of alleles known for a large number of genes such as hemoglobin, cystic fibrosis, hemophilia, G6PD, etc.

Gene Interactions
1. Genes may alter the effect of other genes = epistasis
  - simple example of a multi-step biochemical pathway where absence of an early product makes impossible the production of a later product - e.g. ABO pathway
    or a multi-step developmental pathway - e.g. deaf-mutism
  - more complicated is a dominant inhibition of an early step in a pathway such as in aleurone color in maize
2. Genes may have a quantitative effect
  - snapdragon inheritance showed that 50% enzyme level gave 50% color level resulting in pink rather than red
  - so if an additional allele was added rather than subtracted, one would expect a 50% increase in the intensity of the red color
  - thus, color intensity of seed coat, bark, eyes, or skin is most easily thought of in terms of adding genes where each allele of each gene adds an incremental amount to the final color
3. There may be an environmental interaction
  - some rats have"yellow" fat while others have"white" fat
  - if"yellow" fat rats are fed low levels of carotenoid pigment containing foods, they do not have"yellow" fat
  - "yellow" fat rats are deficient for an enzyme that breaks down carotenoid pigments so the pigments are stored in fat cells

This document maintained by Robert J. Huskey.
Last update on October 27, 1999.