Chapter 22, Problem 20P

In GWAS analysis, because of the existence of LD blocks (or haplotype blocks), it is not necessary to genotype a person for every one of the 50 million known SNPs. Haplotype blocks are stretches of DNA containing particular SNP variants that tend to be inherited together (as a block) because recombination within the region is rare. In the accompanying figure, three different SNP loci are shown at top (SNP10, SNP11, and SNP12), each with two alleles among the world’s population of humans.

Only four of all the possible combinations of these SNP alleles are found in human genomes, as shown in the four chromosome types pictured. These three SNPs are part of a larger block of 20 SNPs that are usually inherited in one of the four configurations, or haplotypes, shown. Because these 20 SNPs are inherited as haplotype blocks, genotyping any individual for the three so-called Tag SNPs (SNP4, SNP8, and SNP15 shown in bold) should be sufficient to predict that individual’s alleles for the other 17 SNPs.

a.	How many configurations of the three SNPs shown at the top of the diagram (SNPs 10, 11, and 12) are theoretically possible?
b.	How many haplotype variants are theoretically possible considering all 20 SNPs in the haplotype block, and assuming that each of them has two possible alleles?
c.	Given that humans are diploid, every individual has two copies of every (autosomal) haplotype block, one on each homolog. Does heterozygosity for the haplotype blocks interfere with genotyping individuals using the Tag SNPs shown in the diagram? Explain?
d.	In part (c), you saw that the three Tag SNPs shown in the diagram are sufficient to type any individual for this particular haplotype block. Is this the only set of three Tag SNPs that could be used?