Why were the principles of population genetics presented in chapters 6 and 7 somewhat of an over simplification?

We only looked at evolution at a single locus, however, many traits are determined by the combined influence of numerous genes.

Why are two loci that are close together considered physically linked?  And what is a multilocus genotype referred to as?  

They are so closely positioned that they usually get carried together during crossing over events. A multilocus genotype is called a haplotype

How do allele frequencies vary between the top and bottom populations in figure 8.2?  Are the populations the same, why or why not?

Allele frequencies are the same. No, they are not the same because the chromosome frequencies differ.

Describe what the terms linkage equilibrium and linkage disequilibrium mean.  

Linkage equilibrium is when the genotype of a chromosome at one locus is independent of its genotype at another. Linkage disequilibrium is when there is a nonrandom association between a chromosome’s genotype at one locus and its genotype at another locus.

The coefficient of linkage disequilibrium. D = gABgab – gAbgaB (D= frequency of homozygotes – frequency of heterozygotes)

In the two locus model, what is important so that the hardy Weinberg conditions are true?

? The same assumptions are true.

Selection on multilocus genotypes, genetic drift, and population admixture

Explain what selection on a multi locus genotype is.

When gene expression at 2 loci has a combined affect acted upon by natural selection. The allele combination between the 2 loci that promotes the best survivorship/reproductive success with increase in frequency.

Genetic recombination (sexual reproduction)

Describe how Clegg Etal. studied the decay of linkage disequilibrium.

Started with 4 pops of flies at complete linkage disequilibrium at loci for enzyme production (Ab and aB at .5 & AB and ab at .5). Random mating decreased linkage over 50 gens.

They don’t work. Single locus studies can be derailed by linkage disequilibrium

California Drosophila melanogaster and Drosophila simulans have reduced genetic diversity along a section of Chr 2. This is because a mutant allele (transposon in front of Cyp6g1) conferred better resistance to insecticides. The allele quickly went to fixation in the population and other alleles around that loci hitchhiked and went to fixation too.

Describe Dawson’s study of linkage disequilibrium on human chromosome 

Surveyed linkage disequilibrium among 1,504 marker loci on Chr 22 in European families. Marker loci were sites showing allelic variation in single nucleotides or small indels. Found that nearby loci do tend to be in linkage disequilibrium with each other in some regions. Linkage disequilibrium is higher when comparing loci of small physical distance.

What is the HapMap consortium?  What have they done?  How have their results compared to Dawson, if at all?

An organization that has assembled a database of over 1 million loci in the human genome with allelic variation at single nucleotides.They look at polymorphic nucleotide loci and look for correlations between certain loci. They have determined complete genotypes at these sites for 269 individuals in 4 populations. Their data confirms Dawsons: linkage disequilibrium falls rapidly with distance between loci

Why would you expect that Arbidopsis Thalina would have high levels of linkage disequilibrium and what did Mangus Nordberg discover?

Arabidopsis typically self fertilizes, which leads to increased homozygosity and reduced opportunity for recombination. Magnus Nordberg discovered that linkage disequilibrium between pairs of loci declines rapidly with the distance between them because Arabidopsis outcrosses enough that its genome resembles sexually reproducing species.

What are 2 practical reasons for studying linkage disequilibrium?

1) Measurements of linkage disequilibrium provide clues that are useful in reconstructing the history of genes and populations

2) Linkage disequilibrium can be used to identify alleles that have recently been favored by positive selection

Why do Ashkanazi Jews have high levels of the 84GG allele of the GBA gene?  When was it estimated that this allele formed and how was this discovered?

Genetic drift acting on chromosomes with loci for 84GG and an 8-repeat in linkage disequilibrium. The 84GG allele probably formed 1,375 years ago. This was found by using the rate of decay and present level of linkage disequilibrium.

Correlation with the history of the people. 100 gen: genetic drift in form of a founder effect accompanying the departure of Jewish populations from the Middle East. 50 gen: founder effect from arrival to central Europe. 12 gen: founder effect from arrival to Lithuania.

What other possible explanation is there for the maintenance of these disease causing alleles in the Ashkanazi?

Possibly selection favoring heterozygotes for at least some categories of alleles.

700 years ago. Short time

The common ancestor for the 32CCR5 allele lived 5,075 years ago and could have increased in frequency so much by genetic drift.

How did Susan Hummel settle the argument?

She confirmed Sabeti’s date by finding several heterozygotes for 32CCR5 in Bronze Age Europeans (2900 years ago) in Lichtenstein Cave.

What did Slatkin and colleagues have to say about whether or not natural selection was involved in the delta 32 CCR5 rise to prominence? What did they base their claims on? 

It could not have achieved its present distribution as quickly as it did without the aid of natural selection.

Why is linkage disequilibrium a good thing for a new allele?

If alleles at the other loci it is linked with are beneficial, it can hitchhike and undergo positive selection with the other loci.

What is the G6PD enzyme and what happens to people with mutations in this enzyme?

Glucose-6-phosphate dehydrogenase. Deficiencies can cause red blood cells to rupture. 

How did Sabeti and Reicht test for positive selection at the G6PD locus in humans? Describe their results. 

They looked to see if the allele had a high frequency and high linkage disequilibrium with other loci. They examined the X chr of African men and looked at SNPs inside and outside of the gene, but nearby. They did an EHH calculation to determine the probability of linkage disequilibrum between loci inside and outside the gene. G6PD-202A had a high freq and high linkage disequilibrum because it had been positively selected for malaria resistance.

Why is lactase persistence good for humans? When did it evolve? How was this discovered?

It allows humans to digest milk sugar and is linked with genes involved with sperm motility and fertilization, olfaction, skin color, skeletal development, and carbohydrate metabolism. It evolved recently (w/in 10,000 years) in Europeans, East Asians, and West Africans. The linkage disequilibrium was discovered using the EHH.

Lactose = Galactose-glucose molecule

Lactase hydrolyses the bond between galactose and glucose.

Lactase persistent people continue to express lactase after infancy.

There was a mutation in the promoter such that there was continuation of lactase production.

Association studies between molecular markers and lactase persistence.

1)   SNPs inside the LCT gene

2)   SNPs in the cis-regulatory regions of LCT

3)   A C/T SNP in a different gene just upstream seems to affect LCT promoter activity

There has been convergent evolution of SNPs in the intron of the nearby gene that affect Transcription Factors/Promoter of LCT