Page 110 - Genetics_From_Genes_to_Genomes_6th_FULL_Part3

404 Chapter 11 Analyzing Genomic Variation

d. At an eighth locus, 1500 reads of a single type of Individual 1:
sequence were found. Provide a possible explana- 5′ CAACGCTTAGGATGTGCGGAGCCT 3′
tion for this result, being as specific as possible. and
5′ CAACGCTTAGGATGTGCGGAGACT 3′
Locus Sequences Number of reads
Individual 2:
1 α: TCTTTGGTAAACGCAAG 1000
5′ CAACGCTTAGGATGTGAGGAGCCT 3′
2 α: GTACCGGAGGCAGCCTC 500
β: GTACCGGCGGCAGCCTC 500
Individual 3:
3 α: AGCCATTGCGGATCCGA 950
β: AGCTATTGCGGATCCGA 50 5′ CAACGCTTAGGATGTGCGGAGCCT 3′
4 α: GGGGCCTTATGATAAGG 50 and
5 α: CAGTTCCTGGAGTTGTA 550 5′ CAACGCTTAGGATGGCGGAGCCT 3′
β: CAGTTCATGGAGTTGTA 450
6 α: GCAGCCCGTGCTGTTAA 500 Individual 4:
β: GCAGCCCGTGCTGTCAA 450 5′ CAACGCTTAGGATGTGCGGAGCCT 3′
7 α: CACTCAGTCCTACGGAC 500 and
β: CACTCGGTCCTACGGAC 450 5′ CAACGCTTAGGATGTGTGGAGCCT 3′
γ: CACTCAGTCCTAAGGAC 50
a. The first exon of the RefSeq copy of this gene in-
cludes the start codon. Write as much of the amino
41. Table 11.2 and Fig. 11.27 together portray the search acid sequence of the encoded protein as possible,
for the mutation causing Nic Volker’s severe inflam- indicating the N-to-C polarity.
matory bowel disease. Neither of Nic’s parents had
the condition, so geneticists narrowed their investiga- b. Are any of these individuals homozygotes? If so,
tion by focusing on rare variants that showed a reces- which person and what allele?
sive pattern and those on the X chromosome. c. Is the inheritance of Brugada syndrome among
a. For candidate variants on an autosome, would the these individuals dominant or recessive?
researchers have looked only for variants for which d. Is Brugada syndrome associated with allelic het-
Nic is homozygous? Explain. erogeneity?
b. Apart from the recessive and X-linked hypotheses, e. Are any of these individuals compound heterozy-
do any other possible explanations exist for Nic’s gotes?
condition? f. Do the data show any evidence for locus heteroge-
c. The causative mutation was pinpointed by analyz- neity?
ing only Nic’s exome, because at the time of these g. Which person has normal heart function?
investigations, whole-genome or whole-exome se- h. For each variant from the RefSeq, describe:
quencing was too expensive to perform on his (i) what the mutation does to the coding sequence;
parents. How could you determine inexpensively and (ii) whether the variation is a loss-of-function
whether or not this mutation occurred de novo in allele, a gain-of-function allele, or a wild-type
the germ line of one of his parents (that is, during allele.
the formation of the particular egg or sperm that
produced Nic)? Your answer should not involve i. For each variant, indicate which of the following
whole-genome or whole-exome sequencing. terms apply: null, hypomorphic, hypermorphic,
42. The human RefSeq of the entire first exon of a gene nonsense, frameshift, missense, silent, SNP, DIP,
SSR, anonymous.
involved in Brugada syndrome (a cardiac disorder
characterized by an abnormal electrocardiogram and j. Is the function of this gene haploinsufficient?
an increased risk of sudden heart failure) is: Explain.
43. Mutations in the HPRT1 gene in humans result in at
5′ CAACGCTTAGGATGTGCGGAGCCT 3′ least two clinical syndromes. Consult OMIM (www
.omim.org) by querying HPRT1; you will only need
The genomic DNA of four people (1–4), three of to look briefly at the top three hits (files #300322,
whom have the disorder, was subjected to single- 300323, and 308000).
molecule sequencing. The following sequences repre-
sent all those obtained from each person. Nucleotides a. What is the full name of the HPRT1 enzyme?
different from the RefSeq are underlined. b. On which chromosome is the HPRT1 gene located?