Applied Genetics 2: Measures of genetic diversity

Variation

occurs at several level in the genome, decreasing in scale from chromosomal anomalies to SNPs

Diversity is only a meaningful concept where there is

Measurable variation in the genome

Population defintion

a group of individuals living in sufficiently close proximity that any member of the group could potentially reproduce with any other member.

Microsatellite

repeating sequences of 2-5 base pairs with variable numbers of repeat units

also known as short tandem repeats (STR) or simple sequence repeats (SSR) or variable tandem repeats (VNTR)

likely involved in variable gene expression

What is a DNA alignment?

Visual way to compare the same portion of DNA from multiple individuals

Where are microsatellites located?

Introns of genes

Single nucleotide polymorphisms (SNP)

locations in genome where a measurable proportion (~2-5% minimum) of the population has one nucleotide and the remainder of the population has another nucleotide

Some SNPs have

functional consequences via non-synonymous subsititution or modification of gene expression, while other don’t appear to have direct consequences

How are SNPs detected?

by sequencing but mostly species-specific SNP chips labeled with DNA probes

Amitraz-resistance SNPs Cause

A change in amino acids from isoleucine to phenylalanine which prevents the binding of amitraz and its metabolites

Beta-adrenergic octopamine receptor (BAOR)

major binding site of octopamine, an essential neurotransmitter in arthropods

Amitraz metabolites also bind and result in loss of function or death

Amitraz-resistance SNPs found in

2010 sequenced the gene in resistant and susceptible ticks in Australia and found common mutation in the BOAR of resistant tick populations

Amitraz-resistance SNPs

2 nearby that confer resistance and 2 in a different transmembrane domain

Haplotypes definition

any combination of alleles at multiple loci on the same chromosome

Having the same halotype means

Two homologous chromosomes share the same allele at each of the loci in question

Having the same halotype means

two homologous chromosomes differ at any one of the loci in question

Distribution of haplotypes on a geographical basis is

very information about evolution history

Haplotypes are created by

Combined SNP, microsatellites and indels at nearby loci (or even anywhere within a single chromosome)

Cryptosporidium parvum haplotypes

pathogenicity is closely linked with haplotypes at several loci.

Multi-locus sequence type

Gene-pool defintion

the total number of all alleles (usually considered in relation to a specific gene or genes)

At each locus

there can be one of several different alleles

Microsatellites for most species and loci

contain somewhere between 5-20 different allelic variants

SNPs contain

2 possible allelic variants

Based on gene frequencies, in an equilibrium population, assuming an infinite population size, no migration, no mutation, no selection and no assortative mating (lots of assumptions that are usually wrong) it is possible to predict

genotype frequencies using the Hardy-Weinberg Law.

Does little genetic diversity always come from inbreeding

Nope

The unit square represents

the total population of gametes

ns meaning

the slight difference from expectation is not likely to be statistically significant

Heterozygosity of the next generation depends on

Heterozygosity of the current generation and the size of the population

Rarer alleles in a population likely will trend to

Be removed from future populations

Hardy Weinberg Law

D + H + R = 1

HWE tests

do not detect mutation

don’t detect the effects of low levels of drift, selection, and migration

Indices for genetic diversity: P

Percentage of polymorphic loci

Indices for genetic diversity: A

Alleles per locus

Indices for genetic diversity: H

heterozygosity

Indices for genetic diversity: N_E

Effective population size

Observed Heterozygosity (H_o):

simply the proportion of all individuals in a population that is heterozygous at the locus in question

Heterozygosity: N

Number of animals in population

Heterozygosity: N_H

Number of heterozygotes

Heterozygosity

H_o = N_H/N

Expected Heterozygosity (H_e) definition

would be expected that if the frequencies of the alleles are similar to each other, then heterozygosity would be higher than if one allele is much more frequent than the other

Expected Heterozygosity

Expected Heterozygosity: N_A

number of different alleles

Expected Heterozygosity: p

frequency of the homozygote for each allele

Alleles per locus

impossible to determine at a give locus in a population without testing entire population

Number of Alleles for SNPs

usually 2 but theoretically could be 4

Number of Alleles for microsatellites

varies, but better markers have 10-15 alleles

Allelic richness

interchangeably with the mean number of alleles at any locus OR

enables compensation for N, the number of individuals tested from the population

Measuring overall genetic diversity with alleles

allele that is rare contributes much less to diversity than an allele that has a high frequency

Heterozygosity is high a any locus in a population when

allele frequencies are equal

many alleles are present at the locus in question

Lower than expected levels of heterozygosity strongly suggest

the random sampling effects of genetic drift (including founder effect) have been strong or there is assortative mating

Alleles at any locus over sufficient time is expected to

either be lost from or become fixed at that locus in that population

Wright’s equation

predicts the change in the frequency of heterozygotes (H) from one generation (g) to the next (g+1) for a population of N individuals:

Heterozygosity is always expected to

decline in a closed population without selection

Real populations of animals

don’t usually conform to the assumptions of random selection of gametes and random mating

Animals tend to choose mates

that are more similar to them (positive) or more different (negative)

Sex ratios often deviate from 0.5 and mating is assortative (+ or -)

Effective population size definition

the size of the ideal population that would lose heterozygosity at the same rate as an actual population of interest

Effective population size

very sensitive to deviations from a 0.5 sec ratio and is estimated with equation