Polygenic traits, heritability

continuous phenotypic variation vs categorical medelian variation

categorical: white or red populations

continuous: number, quantitative, describes populations, follows bell cuve

• degree of pigmentiation in skin, mating calls, diseases

polygentic trait

multiple genes that contribute to single quantitative trait

can mendelian inheritance produce a continuous phenotype

yes, with two or more gene

what smooths out the curve

effects of environmental variation

when can u infer polygenic inheritance

when a trait exhibits continuous variation and its distribution in a population forms a bell-shaped curve

variance

phenotype variance in population

additive allelic inheritance

the more domiance (AABb), the more gene dosage, get a range of values (skin color, hair color)

incomplete dominance is a case of ___ where only _ gene locus is invovled

additive inheritance, one RR (red) + rr (white) → Rr (pink)

Vx= Vg+ Ve describe

vx= phenotype variance

vg= genes (0 if inbred)

ve= environment (0 if controlling temp, diet)

what is the equation for heritability, describe relationship between Vg and Ve

if high Ve= low heritability

concordance- mono and dizygotic

what extent do siblings share particular phenotype?

mono: 100, share, dizygotic: 50

heritability

proportion of population variation that is due to genetics

why are twins useeful in studying heritability

monozygontic (identical twins) share 100% of genes + same environment

dizygotic (fraternal) share 50% of genes, share same environment

• If MZ twins are more similar than DZ twins, this suggests that genes play a strong role.

• If MZ and DZ twins are equally similar, this suggests that environmental factors are more important.

if heritability = 1 (all variations due to genetics) then monozygotic is

if heritability = 0 then mono and dizygotic

100% concordance

low concordance

make argument for a trait with low heritability, “genes don’t matter” for that trait or that “the phenotype is determined by the environment”. having fingers

Having fingers is entirely determined by genes, but because nearly everyone has 10 fingers, there’s almost no variation in that trait — so heritability is low, even though genes clearly matter.

high concordance _ high heritability

DOES NOT EQUAL

but concordance + shared and unshared environment = heritability

how often two individuals, typically a pair of twins or relatives, will share a particular trait or condition

limitations to heritability estimates, common ways they are misinterpreted

.88 means 88% of phenotypic variation is caused by genetic variation

1. “If H² low, genes aren’t important” heritability DOES NOT EQUAL inheritance because H^2 refers to POPULATION

• environmental variance is high (milk development in cows, genes play role in milk development, but also very dependent on environment)

2. family studies over-estimate heritability because environment similar

low heritability

few alleles in population

low proportion of phenotypic variance is due to genetics

largely due to environment

high heritability

many alleles in population, minimal environmental effect

heritability does NOT

\equal fate

• stays same if environmental changes

  • mean that group differences are genetic

heritability determines if

• determine whether nature/ nurture is more important

• inform doctors how much family history will predict patient outcome

• determine whether drug treatment/ behavior modification are more successful in treating disease

haplotype

specific combination of SNPs (single nucleotide polymorphism) across loci (specific gene location) on same chromosome

haplotype block

group fo SNPs that are inherited tgt- if on same block linkage disequilibrium,

• will find together more,

• no recombination- preserved and frequently inherited

• a non-random association of alleles at different loci on a chromosome,

• Pa= 0.5, 0.5, 0.5, 0.5

• Pab 0.5, 0, 0, 0.5

if on different block- linkage equilibrium (inheritance of one gene does not influence the inheritance of another)

• Pa= 0.5, 0.5

• Pab= 0.25, 0.25

evolutionary creation of set of haplocytes

• Mutations: Novel haplotypes often originate from polymorphism mutations.

• Recombination: during meiosis breaks down ancestral haplotypes and shuffles genetic material, leading to new combinations of alleles.

• Gene Flow: The movement of genes between populations through migration and interbreeding can introduce new haplotypes and alter existing haplotype frequencies.

• Natural Selection: A haplotype with a genetic advantage that increases an organism's survival and reproduction (fitness) will become more common in the population.

what are the main uses for haplotype blocks

• make scanning genome easier

• different SNPs in those affected, helps pinpoint disease causing mutations

  • certain SNPs are associated with population

what does mahattan plot tell

The higher the dot on the plot, the stronger the association of that genetic variant with the trait or disease. 

how to show that gene identified in GWAS study is gene causing disease, becase it only tells coorelation

1. sequence gene w unaffected vs affected individuals can narrow down mutation

2. determine gene is expressed in unaffected and affected using rna gel

3. determine function of gene thru LOF knock out

limitations of GWAS

small sample size, small population stratification, shared evironmental factors (socioeconomic), rare variants go undetected