genetic variation and analysis

Question 1

population genetics

Answer 1

investigates genetic variation among individuals within and between groups
genetic basis for evolutionary change
how patterns vary geographically over time
applicable to all kinds of populations

Question 2

human populations

Answer 2

demographic structure
genetic structure- genes that we possess
constitution- how many alleles are in the population + how the genes are passed on
continuing entity

Question 3

genomic variation

Answer 3

mutations are pimary source- dna sequence/genes/repeat size/chromosome numbers
genetic variability is the raw material upon which natural selection operates
can occur at all levels- from micro- change in one letter of dna sequence
locus- location of dna sequence/ gene in genome
allele- different forms of same gene or dna sequence

Question 4

specific loci

Answer 4

ABO locus- A, B, O alleles- has 4 phenotypes and 6 genotypes
A,B codominant, O is recessive
beta hb locus- S,C,C
SNP locus- A + G or C+T - or any combination
repeat loci-2-2 or 3-4 repeats- alu, II,ID,DD
insertion deletion

Question 5

genetic constitutions

Answer 5

a pool of genes/alleles at any one time
can be specified in the form of allele frequencies
allows comparison- uni dimensional (one population), multidimensional (different population groups/ethnicities)
admixture- when 2 populations mix, offspring will have genetic makeup of mixture of migrating and receiving populations

Question 6

genetic structure

Answer 6

the way alleles are distributed and combined with populations
human populations are heterogenerous
barriers to breeding/mating- cultural, religion or social
subdivisions affect distribution of genes within populations, lead to consequences –> divergence, fixation of genes at a locus, increased homozygosity

Question 7

maintenance of genetic variation

Answer 7

errors in dna replicationa are not always repaired by the mechanisms - leads to mutations
some alleles may not be independently assorted
haploid gametes- crossing over (variation)

Question 8

allele frequency calcs

Answer 8

SNPs, alu, STRs
eg 2 alleles I and D
homozygotes and heterozygotes
- I allele = (2 Homozygotes) + Heterozygotes/ 2*N
*1st allele = p, 2nd allele= q
if there are 2 alleles then p+q=1
any numbers of alleles, formula should work and still add up to 1)

polymorphisms will usually have 2 polymorphisms- insertion and deletion allele

Question 9

SE of allele frequency

Answer 9

allows evaluation of range and calculation of CI
SE and SD are the same for allele frequencies
√p x(1-p) / 2xN
p= allele of interest
N= no. of individuals in study
small samples have larger SE
for 2 allele systems (alu/snps)- SE same for both alleles
STRs- multialleic systems- each allele has separate SE
SE low is good

Question 10

heterozygosity

Answer 10

how many heterozygotes are in a population
observed heterozygosisy- frequency of the heterozygotes - h=nh/N
Where nh is the number of heterozygote individuals and N is the total number of individuals studied/analysed
expected heterozygosity= H=1-sum of p^2
p= allele freqency,

1- exp homozygosity= expected heterozygosity

Question 11

HWE

Answer 11

in a large random mating population, allele and genotype frequencies do not change from 1 generation to next
assumptions
- random mating
- infinite population size
- no mutation or selection
- no migration
cant be used for humans
formula- (p+q)2 = p2+2pq+q2

Question 12

how and why do we test hwe

Answer 12

tested within the population
null hyp= there is no difference between observed and expected genotype frequencies
population maintains hwe or population does not show departure/deviation from hwe

1. calculate allele frequencies
2. work out expected genotype frequencies
3. work out expected genotype numbers
4. use chi2 to test null hypothesis

Question 13

HWE explained

Answer 13

HWE is calculated for each locus and each population
if not maintained, assumptions causing changes to allele frequencies need evaluation
could be due to selection, gene flow + migration, inbreeding, genetic drift and founder effect, mutation

Question 14

genetic differences between populations

Answer 14

multiple usages (group comparisons/case control disease analyses)
categorical data
simple solution- compare genotype and allele frequencies using descriptive methods

Question 15

statistical comparisons

Answer 15

using rxc contigency chi square methods (multidimensional chi square)
organise data into columns + rows, work out totals
work out expected numbers from observed data and work out chi2 for whole table
- expected number = (row totoal * column total)/grand total
- work out expected values for each cell – work it out individually
- degrees of Freedom = (Number of Columns -1) * (No of Rows -1)

Question 16

quantifying genetic differences - Fst Gst statistic

Answer 16

variation within sub population is high- variation between sub population is zero= Fst = 0
cannot predict which sub pop an individual will belong to

variation within sub pop is low (0)- variation between sub population is maximised= Fst=1
can predict which sub population an individual belongs to

Question 17

gene diversity analysis

Answer 17

based on:
Hs= average heterozygosity
Ht= heterozygosity of total population
Dst= Ht-Hs
Gst= (Ht-Hs)/Ht
coefficient of gene differentiation
high Gst values are indicative of higher differentiation (inbreeding and isolation)=

Question 18

genetic distance

Answer 18

degree of relationship by descent between 2 individuals/ populations
difference between populations are multidimensional- difficult to describe descriptively
many measures available
different assumptions and conmputational requirements
allows construction of trees- dendrograms

Question 19

neils d

Answer 19

one of the simplest genetic distance measures, probability that a random chosen allele from each of the two populations will be identical, relative to the probability that 2 randomly chosen alleles from the same population will be identical

Question 20

neils d calculation

Answer 20

D = - ln I
where I = [Σxiyi / (Σxi2 Σyi2)0.5 ]
in is natural log

assumptions
- infinite allele model 
- all loci have same rate of neutral mutation 
- mutation- genetic drift equilibrium and stable effective population size