Topic 5 - Mendelian Extensions

Variation on dominance

Complete dominance, Incomplete dominance (blending), Co-dominance, Allelic series, Lethal allels, Penetrance and expressivity

Complete dominance

Mendel expirement,F1 all dominant phenotype, F2 3:1 phenotypic ratio, dominant allele(only 1 needed) mask phenotypic expression of recessive

Haplosufficient

only need 1 copy of allele to produce enough product, recessive mutation result in no product being made

Haploinsufficient

dominant mutation, one copy not enough

null mutations

produces nonfunctional proteins

Dominant negative

proteins produce inhibits wildtype protein

Incomplete dominance

phenotypic ratio differs, bc allelic interaction, heterozygous phenotype is distinct, looks like blending, F1 generation do not produce dominant phenotype, F2 ratio of 1:2:1

Codominance

heterozygous phenotype is distinct, detecable expression of both alleles (no blending), production of both proteins

ABO blood type system

Codominance (A and B codominant and dominant over O), 4 types (AB/A/B/O), identified by antigen-antibody reaction, surface antigen of RBC

MN blood type system

Codominance, surface antigen of RBC, 3 types (M/N/MN), assort independently of ABO

Allelic series

multiple alleles (>2), order of dominance based on amout of protein produced, # genotypes = n(n+1)/2, # homozygotes = n, # heterozygot = n(n-1)/2

C gene

Coat colour, polygenic (multiple genes) with multiple alleles, focus 4 (C> Cch< Ch<c), production of tyrosinase

C gene C- allele

dominat to all other, wildtype coat colour

C gene Cch allele

reduced colour bc reduced production of tyrosinase, chinchilla phenotype, almost codominant with Ch

C gene Ch allels

fully pigmented extremities, temperature sensitive (away from core produces), Himalayan phenotype, almost codominant with Cch

C gene c allele

recessive to all other, complete lack of enzymatic activity, albino phenotype

Lethal alleles

mutation in essential genes, death if homozygous, recessive is rare and hidden by dominant phenotype

Dectection of lethal alleles in mammals

distortion to Mendelian expect proportion (expect 3:1 but 100% dominant)

Dectection of lethal alleles in plants

embryos dying, fail to produce gametes with lethal alleles

Agouti gene

lethal allele in mice, both dominant gene but homozgyous Agouti lethal, F2 ratio of 2:1

Tay-Sach disease

lethal allel in humans, autosomal recessive, lack enzyme to break down lipid (especially in brain/nervous system), CNS break down, life expectancy 3-4 yrs

Huntington disease

lethal allele in humans, autosomal dominant (lethal homo or heterozygous), neuromuscular disease,fatal 10-15 after diagnosed, mutation at end of chromosome 4, delayed age of onset (able to reproduce before death)

Complete penetrance

genotype always produces same phenotype

Incomplete penetrance (non penetrance)

phenotypic variation, cause by environmental or genetic influence

Penetrance

percentage of individuals with given allele to exhibit the phenotype

Variable expressivity

same genotype produces variable phenotype due to varying expression of the alleles

Gene-enviroment interactions

Sex(hormone), temperature(enzymes), age(cell functioning), chemical and diet, pathogens/parasite exposure (allergies)

Pieiotropy

alter multiple features in phenotype from single gene mutation

Allergies and genetics

strong genetic influence, immune system mutation - increase allergy risk

incidence of allergies

higher in developed countries, higher in first borns, lower in larger families, lower in daycare kids, lower in rural famillies, “hygiene hypothesis”

reason for increase allergies

immune system haven’t been exposed (undereducated)

Canadian guideline to pregnancy diets

no restriction of maternal diet, exclusve breastfeeding/formula for 6 months, allergenic food exposure at 6 months

One gene one polypeptide hypothesis

Beadle and Tatum, single gene mutation results in phenotypic change

Prototrophic/prototroph

refers to wildtype

Auxotophic/auxotroph

refers to mutant

Beadle and tatum experiment

irradiated wildtype Neurospora, grow on different mediums (growth medium the minimal media), transferred auxotroph into various supplemented media (if grown known missing nutrient)

testing for genetic interaction

obtain single gene mutation (test dominance), test mutant for alelism(multiple loci?), combine mutants (form double mutant) see if genes interact

determine if genetic interaction

from phenotype of double mutant, differs from simple combination of both single gene, modified mendelian dihybrid phenotype ratio

complementation test

determine if 2 mutant are on same gene or different gene, map the chromosomes, cross 2 homozygous for different recessive mutants

results form complementation

if progeny has wildtype - mutants on different chromosomes, if progeny doesn’t have wildtype - mutants on same gene

phenotype of F2 generation if no genetic interaction with complete penetrance

mendelians 9:3:3:1

phenotype of F2 generation if complementary gene action

9:7, need both functioning genes to produce single product

phenotype of F2 generation if duplicated gene action

15:1, only need one functioning gene to produce product, onlyhomozygous recessive at both produces recessive phenotype

phenotype of F2 generation if dominat gene interaction

9:6:1, need dominance at both for full phenotype

phenotype of F2 generation if recessive epistasis

9:3:4, homozygous recessive genotype at one mask expression of other

phenotype of F2 generation if dominant epistasis

12:3:1, dominat allele at one mask expression of other 

phenotype of F2 generation if dominant suppression

13:3, dominant allel supreesses (inhibit) expression at other locus

Tricks for modified mendelian ratios

>4 phenotypes - >1 trait(Codominace or incomplete), <4 phenotypes - 1 trait (genetic interaction)