Page 107 - Genetics_From_Genes_to_Genomes_6th_FULL_Part3

Problems 401

the disease gene, the linked SNP loci, and the two 30. Now consider a mating between consanguineous peo-
crossovers. Your map should indicate any uncer- ple involving a recessive genetic disease. The figures
tainties in these positions. that follow show the genotypes of these two people at
f. Diagram the location and arrangement (phase) of four SNP loci (1–4).
all alleles of all genes that are on the two chromo-
somes in the father’s diploid genome. Locus 1 Locus 2 Locus 3 Locus 4
28. The figure that follows shows the pedigree of a family AT TT GG TT AC AC CC CG
in which a completely penetrant, autosomal dominant
disease is transmitted through three generations, to-
gether with microarray analysis of each individual for
a biallelic SNP locus (the alleles are C and T).

a. For which of these loci is it possible to obtain in-
I formation about the linkage of the SNP to the dis-
1 2 ease gene? Explain your answer for each locus and
II
1 2 describe any special conditions that may apply.
III b. For any of the loci for which the mating is poten-
1 2 3 4 5 6 7 8
tially informative, how would you tell whether the
IV child is the product of a recombinant or nonrecom-
1 2 3 4 5 6 7
binant gamete? (That is, how could you solve the
I II III IV
phase problem?) Be as specific as possible.
31. The pedigree shown in Fig. 11.22 was crucial to the
identification of the Huntington disease gene HD,
which is located on chromosome 4.
a. Do the data suggest the existence of genetic link- a. The data show that the DNA marker G8 is clearly
age between the SNP locus and the disease locus? linked to HD. For the large majority of the people
If so, what is the estimated genetic distance be- in the pedigree with Huntington disease, which
tween the two loci? allele of G8 (A, B, C, or D) did they inherit, along
b. Calculate the maximum Lod score for linkage with the dominant disease-causing allele of HD,
between the SNP and the disease locus for this on the copy of chromosome 4 from their affected
pedigree. What does this value of the Lod score parent?
signify? b. How many people in the pedigree can you catego-
29. One of the difficulties faced by human geneticists is rize absolutely as the product of parental or recom-
that matings are not performed with a scientific goal binant gametes from their affected parent, without
in mind, so pedigrees may not always provide desired making any assumptions at all (including the as-
information. As an example, consider the following sumption of linkage)?
matings (W, X, Y, and Z): c. If you now make the assumption that G8 and HD
are linked, how many of the people in this pedigree
MATING W MATING X MATING Y MATING Z must be the product of a recombinant gamete from
their affected parent?
A1A1 A1A2 A2A5 A2A3 A2A2 A1A5 A1A1 A3A3
B3B4 B4B4 B1B2 B2B3 B1B4 B3B3 B2B2 B4B4 d. Based solely on the data from this pedigree, what
would be the best estimate for the map distance be-
tween G8 and HD?
e. Considering your answers to parts (b) through (d),
calculate the maximum Lod score. The pedigree
a. Which of these matings are informative and contains 47 people resulting from informative mat-
0
which noninformative for testing the linkage ings. (Note that 0 = 1.) What does this Lod score
between anonymous loci A and B? (A1 and A2 signify?
are different alleles of locus A, B1 and B2 are dif- 32. You have identified a SNP marker that in one large
ferent alleles of locus B, etc.) Explain your answer family shows no recombination with the locus causing
for each mating. a rare hereditary autosomal dominant disease.
b. Is locus A more likely to be a SNP or an SSR? Furthermore, you discover that all afflicted individu-
What about locus B? Explain. als in the family have a G base at this SNP on their