Population Genetics

Question 1

Polymorphic Alleles/ Polymorphic vs. Nonpolymorphic Alleles

Answer 1

• -allele variants that are present in more than 1% of population
• -some genes (HLA) are very polymorphic and polymorphisms determine individual characteristics
• -other genes like histone encoding genes are not because any mutation in these is incompatible with life

Question 2

Extent of polymorphisms

Answer 2

• -6,000,000 single nucleotide polymorphisms (SNPs) between unrelated inidividuals (0.1% of genome)
• -SNP’s = genetic variation and they do NOT cause disease
• -3 deleterious recessive mutations per individual
• -90% of worlds SNP can be found with any given population (only 10% of SNPs truly set asians apart from Europeans)

Question 3

Characteristics of Ideal Population for Hardy-Weinberg

Answer 3

• -large population size
• -equal fitness of offspring
• -random mating
• -no influx of new alleles
• -however, populations are not ideal
• -model predicts that allele frequencies in population will not change over time

Question 4

Hardy-Weinberg equations allows you to calculate?

Answer 4

• -carrier frequencies when given frequency of an allele in gene pool
• -OR, frequencies of alleles in gene pools when given carrier frequencies

Question 5

Formula for carrier frequency in recessive disease

Answer 5

= 2 * square root (prevalence)

Question 6

Allele Frequency in X-linked recessive diseases formula?

Answer 6

– males affected / total males in population

Question 7

nonrandom mating does NOT affect allele frequency over time but what does it affect?

Answer 7

• -will affect how many individuals are homozygous or herterozygous for a mutation
• -

Question 8

Real populations are in disequilibrium because of?

Answer 8

• -genetic drift
• -selection
• -assortative mating
• -bottleneck and recovery

Question 9

Genetic Drift

Answer 9

–small populations, genetic drift can lead to disappearance or multiplication of rare alleles, w/o any selection for or against that allele

Question 10

Selection

Answer 10

• -over time, will reduce number of detrimental mutant alleles in population, will stabilize at low levels though
• -reduces frequencies of alleles that reduce fitness
• -state of equilibrium = loss of mutant alleles = spontaneous occurrence of new mutant alleles
• -dominant alleles disappear quickly
• -recessive alleles disappear very slowly since they can “hide” in heterozygotes
• -all of the above is negative selection
• -positive selection = mutant alleles that give advantage to those that carry them, when they are heterozygotes (think of malaria and sickle cell trait)

Question 11

Assortative mating

Answer 11

• -selection of partners based on a specific genetic trait
• -disturbs equilibrium distribution of alleles
• -increases the degree of homozygosity in a population beyond what is predicted by HWequations
• -NOTE: consanguineous matings do not change allele frequency in gene pools–only change is an increase in homozygote frequency beyond expected level

Question 12

Founder Effect

Answer 12

• -small founder population can lead to amplification of rare alleles
• -in small population, inbreeding is common, which only increases fractions of those that are homozygous for rare allele

Question 13

Ellis van Creveld Syndrome

Answer 13

• -rare recessive mutation in EVC gene amplified by founder effect (amish peeps)
• -consanguineous matings were inevitable so that increased number of those w/ rare allele
• -skeletal dysplasia, shortening of forearms and lower legs, postaxial polydactyly and heart defects
• -carrier of EVC mutation is now 12.3% in Amish people of that area, (only 0.8% in general population)

Question 14

Genome wide analysis of polymorphisms shows?

Answer 14

• -that 90% of variation is between individuals and not between races
• -therefore, race isnt a good predictor for individual drug response

Question 15

Genome wide association studies

Answer 15

• -compare SNP’s between Pts. and controls
• -calculate odds ratio for each SNP and associated disorder
• -find SNP’s that are strongly associated w/ disease

Question 16

Linkage Equilibrium vs. Disequilibrium

Answer 16

• -Equil: in population, two close markers are associated half of the time
• -Disequil: in population, two close markers are associated much MORE frequently than expected (50%) by chance

Question 17

How are alleles that contribute to certain disease found?

Answer 17

• -they look for linkage disequilibrium between easily tracked markers and a disease phenotype to locate disease allele
• -best to use genetically young and small populations
• -fewer meioses have occurred so less likely the markers was separated from diseased allele
• • small pops. because it is likely that every individual suffering from disease has same mutant allele

Question 18

Steps in finding mutations that (Ex.) increase risk for type 1 diabetes

Answer 18

• -find small, young, genetically isolated pop.
• -assume founder effect
• -assume linkage disequilibrium: marker that was close to mutation in founder is still linked
• -scan genomes for markers that are shared by all affected individuals