Lecture 1.5 Non-Mendelian Inheritance

Factors that alter single-gene phenotypic ratios

multiple alleles, incomplete dominance, codominance, epistasis, expressivity, pleiotropy, phenocopy, and genetic heterogeneity

t/f most genes exhibit simple inheritance

false

Ataxia

describes a lack of muscle control or coordination of voluntary movements

Friedreich’s ataxia (FRDA)

most common autosomal recessive ataxia. Caused in almost all cases by homozygous intronic expansions resulting in loss of frataxin.

What causes friedreich’s ataxia?

expansion of GAA repeats in intron 1 of the FXN gene

Frataxin

nuclear encoded mitochondrial protein involved in mitochondrial iron homeostasis

How does Friedreich’s ataxia show pleiotropy

it affects multiple organs; affects the nervous system, heart, pancreas and muscles

Lethal genotype

causes death before the individual can reproduce. Removes an expected progeny class following a specific cross. May be caused by double dose of a dominant allele

A — of a — allele can be lethal (as seen in achondroplastic dwarfism)

double-dose; dominant

Achondroplastic dwarfism

genetic condition that is the most common type of short-limbed dwarfism. Lethal if homozygous dominant.

Multiple alleles

individuals with different mutant alleles create many variants of degrees of a phenotype are possible. Example is cystic fibrosis

Compound heterozygotes

individuals with different mutant alleles for a gene that has multiple alleles.

Cystic fibrosis

genetic diseases with varying degrees of phenotypes due to CFTR gene having multiple(over 1500) mutant alleles

Incomplete dominance

heterozygous phenotype is intermediate between those of the two homozygotes

Familial hypercholesterolemia

genetic disorder which displays incomplete dominance where heterozygotes exhibit about half of LDL receptors in liver than normal while homozygotes for the mutant allele lack the receptor causing high serum cholesterol levels.

Codominance

a heterozygote’s phenotype is distinct from and not an intermediate between those of two homozygotes. Expression of both alleles

iA allele

produces A antigen

iB allele

produces B antigen

i allele

does not produce an antigen

IA and IB are — and both are completely dominant to —

codominant; i

Possible allele combination for individuals type A blood

IAIA or IAi

Possible allele combination for individuals type B blood

IBIB or IBi

Possible allele combination for individuals type AB blood

IAIB

Possible allele combination for individuals type O blood

ii

epistasis

when one gene masks or affects another’s phenotype

Bombay phenotype

H gene is epistatic to I gene. H protein places a molecule at the cell surface to which A or B antigens are attached.

hh (bombay) genotype results in

no H protein and A or B antigens cannot be attached to the surface of RBC. gives the phenotype of type O , although ABO blood group may be anything.

Penetrance

all-or-none expression of a single gene. Some individuals with a particular genotype do not have the associated phenotype.

Polydactyly is autosomal dominant but is not expressed in some cases when individuals have the allele. Why?

incomplete penetrance

Genotype is incompletely penetrant if

some individuals do not express the phenotype

Expressivity

genotype is associated with a phenotype of varying intensity.

Phenotype is variably expressive if

symptoms vary in intensity among different people with the same genotype

Repeat expansion diseases

example of expressivity. Diseases are more severe the more repeat expansions that the individual has.

Anticipation

seen in repeat expansion diseases. Increase in severity of the disease and decrease in age at onset from one generation to the next as the number of repeats increases.

Pleiotropy

phenotype includes many symptoms, with different subsets in different individuals. Gene controls several functions or has more than one effect.

Marfan syndrome

autosomal dominant disorder in which mutations in the gene FBN1 affect the ocular, skeletal and cardiovascular systems.

MC1R

gene wich exhibits pleiotropy as a variant can result in a phenotype for red hair, pale skin, freckles, and susceptibility to skin cancer

Phenocopy

an environmentally caused condition has symptoms and a recurrence pattern similar to those of a known inherited trait. Appears inherited but is caused by environment

Examples of phenocopy

teratogens like thalidomide (chemicals that cause birth defects) and HIV (may be passed from mother to child, appearing inherited)

Genetic heterogeneity

different genes produce identical phenotypes

Hearing loss may be caused by — different autosomal recessive forms. This exhibits —

132; genetic heterogeneity

Genetic heterogeneity may result from genes that encode enzymes which —- or different proteins that are —

part of the same biochemical pathway (both blanks)