Extensions of Mendelian Genetics

Definition: Inheritance patterns that obey Mendel's two laws:
- Law of Segregation: Each individual carries two alleles for each trait, and these alleles segregate during gamete formation.
- Law of Independent Assortment: Alleles of different genes assort independently of one another during gamete formation.
Simple Mendelian Inheritance: Cases in which the observed genotypic and phenotypic ratios easily follow Mendel's laws.
- Traits controlled by a single gene with two different alleles — one allele is dominant, while the other is recessive.
Most traits in nature do not exhibit simple dominant-recessive relations.

Wild Type: The most common allele(s) in a population, associated with a "normal" phenotype.
Polymorphism: The existence of multiple wild-type alleles in a population.
Mutant Alleles: Result from random mutations in existing alleles; these are typically less common and can have good, bad, or neutral effects, often inherited recessively.

A recessive allele does not affect the phenotype of a heterozygote.
Wild-Type Phenotype Explanation:
- The heterozygote may produce normal protein levels above the threshold requiring for function (≥ 50%).
- The normal gene may be up-regulated to compensate for the defective allele.
Loss of Function Mutations: Result in reduced production of functional protein.

Gain of Function Mutation: Results in a new (neomorphic) or abnormal (increased or hypermorphic) function.
Dominant Negative Mutation: A mutant protein counteracts the normal protein, making it nonfunctional (antimorphic).
Haploinsufficiency: Heterozygotes cannot compensate for a loss of function mutation, leading to a phenotype.

Incomplete Dominance: A heterozygote displays an intermediate version of the dominant phenotype.
- Example: C₁C₂ represents a scenario where 2 copies of the dominant allele are required for full expression.
- The observed phenotypic ratio in a cross of these alleles is 1:2:1.
- A null allele results in the total loss of gene function.
Codominance: Both phenotypes are expressed simultaneously in the heterozygote, retaining a 1:2:1 phenotypic ratio.

Example: ABO blood group involves three alleles: Iᵃ, Iʷ, and Iᵇ, with Iᵃ and Iᵇ being codominant.
Overdominance (Heterozygote Advantage): Heterozygotes may have a selective advantage.
- Example: In sickle cell anemia, heterozygotes are resistant to malaria and do not suffer from sickle cell symptoms.

Example: Siamese cats having color that changes due to temperature variations early in life.
Norm of Reaction: The range of phenotypic expressions associated with a particular genotype under varying environmental conditions.

Traits governed by genes located on sex chromosomes (X and Y).
- X-Linked Recessive Inheritance: Mostly affects males, with females often being carriers.
- Males have one copy of the X chromosome, while females have two.
- For most sex-linked genes, reciprocal crosses yield distinct results, aiding in determining if a gene is sex-linked.

Wild type is common in populations.
Hemizygous: Males are hemizygous for genes on the X chromosome and do not have a paired allele.
Reciprocal Cross: A method to ascertain if a gene is sex-linked.
X-Linked Dominant Inheritance: Affected males pass the trait to all daughters but not to sons.
Y-Linked Inheritance: Transmitted from father to son, with relatively few genes in humans.

Short regions of homology on X and Y chromosomes that allow pairing during meiosis.
Genes in these regions exhibit inheritance patterns typical of autosomal genes.

Sex-Influenced Inheritance: A trait is dominant in one sex and recessive in another.
- Example: In cattle, the presence of scurs is dominant in males and recessive in females.
Sex-Limited Inheritance: A trait expressed only in one sex, often influenced by sex hormones or sex-specific pathways.
- Example: Male feather patterns in birds occur only in the presence of low estrogen levels.

Two copies of a lethal allele lead to death; e.g., in Manx cats.
The Manx allele is dominant concerning the presence/absence of a tail, but homozygosity is lethal.
Pleiotropy: One gene can affect multiple traits, seen in both recessive lethal alleles and conditions such as Huntington's Disease.

Gene Interactions: When multiple genes influence the outcome of a single trait, which differs from pleiotropy.
Recessive Epistasis: A homozygous recessive genotype at one locus masks the expression of the gene at another locus.
- Example: Mice coat color affected by Agouti and Black loci, where homozygous recessive at the black locus results in white mice regardless of other genotype influences.
Phenotypic Ratio: The intercross of a dihybrid (AaBb) leads to a phenotypic ratio of 9:4:3.

Gene Redundancy: One gene can compensate for the loss of function of another.
- Example: In a gene where a dominant allele produces triangular seeds; the phenotypic ratio could be 15:1.
Complementation: Producing wild-type offspring phenotypes from parents with similar recessive phenotypes.
- As long as there is one dominant allele for each gene, the result will be dominant wild-type phenotype, yielding a phenotypic ratio of 9:7.

Offspring phenotype is determined by the mother's genotype, regardless of the father's genotype.
- Example: Shell coiling in snails shows differing outcomes based on maternal genotype regardless of paternal contribution.

Phenotype determined by maternal alleles through organelle inheritance.
- Mitochondrial DNA (mtDNA) is not on chromosomes and affects offspring irrespective of their sex, as mitochondria are maternally inherited.
Heteroplasmy: Cells possess a mixture of organelles with different genotypes due to mitochondrial DNA not being sorted evenly.

A null hypothesis states the expected Mendelian ratio for genetic traits. If statistical analysis shows p < 0.05, one would reject the null hypothesis, indicating a non-Mendelian pattern of inheritance.