Chapter 10, Problem 24P

The microarray shown at the top of this page analyzes genomic DNA from a nuclear family in which the father, one son, and one daughter have rare, late onset polycystic kidney disease; while the mother, the second son, and the second daughter are unaffected. As stated in previous problem, the eight SNP loci examined are evenly spaced at about 10 Mb intervals on chromosome 4, and they are shown on the microarray in their actual order on this chromosome.

a.	Is the allele responsible for the disease dominant or recessive with respect to wild type? Is the disease gene autosomal or X-linked?
b.	For each of the four siblings, indicate the genotype of the sperm from which they were created. For each of these sperm, write the alleles for each of the eight loci on chromosome 4 in order.
c.	Identify the two SNP loci that are uninformative in this family (that is, you cannot determine whether or not either of these loci is linked to the disease gene).
d.	Assuming for the sake of simplicity that the four children shown would be completely representative even if the parents had 100 children, the data in the figure indicate that one locus is unlinked to the disease gene. Which one?
e.	The microarray results indicate that during meiosis in the father, two different crossovers occurred in the region including the disease gene and the SNP loci that are genetically linked to it. Draw a map of chromosome 4 showing the locations of the disease gene, the linked SNP loci, and the two recombination events. Your map should indicate any uncertainties in these positions.
f.	Diagram the location and arrangement (phase) of all alleles of all genes that are on the two chromosomes in the father’s diploid genome.

Summary Introduction

a.

To determine:

Whether the allele responsible for the disease is dominant or recessive concerning wild form and whether the disease gene is autosomal or X-linked.

Introduction:

The alleles that reveal their effect even if the individual only has one copy of allele are known as dominant alleles.

Explanation of Solution

The allele that is responsible for the disease is an autosomal dominant allele. Autosome refers to the non-sex chromosome, and the term dominant signifies that a single copy of disease-associated mutation can cause disease.

Summary Introduction

b.

To determine:

The genotype of the sperm from which the four siblings were formed and for each sperm, order the allele for each of eight loci on chromosome 4.

Introduction:

The male reproductive organs called testes releases sperms. A genotype is the set of genes in the DNA (deoxyribonucleic acid) which causes a particular trait.

Explanation of Solution

Allele and loci	1	2	3	4	5	6	7	8
Affected father	CA*	GG*	GA*	TG*	CC	GC*	GA*	TG*
Unaffected mother	AA	GC	GG	AT	CC	CC	AG	TT
Affected son	CA*	CG*	GA*	AG*	CC	CC*	AA*	TT*
Affected daughter	AA*	GG*	GA*	TG*	CC	CC*	AA*	TG*
Unaffected son	AC	GG	AG	TT	CC	CG	GG	TT
Unaffected daughter	AA	CG	GG	TT	CC	CG	GG	TT

Alleles with asterisk superscript denote disease associated alleles. Alleles shown in red indicate the genotype of sperm from which the siblings were formed.

Summary Introduction

c.

To determine:

The way to prove that the loci are on chromosome 4 and are 10 Mb apart.

Introduction:

The mating that reveals the inheritance or linkage relationships of a gene or an allele is referred to as informative mating.

Explanation of Solution

For mating to be informative, the loci must be heterozygous in key individuals. If both parents are heterozygous, meiotic events can be easily reconstructed by studying the offspring genotypes. The loci 4 and 7 are heterozygous and are informative, of which allele is inherited from which parent.

Summary Introduction

d.

To determine:

The locus that is unlinked to the disease gene.

Introduction:

Linked gene refers to the genes whose alleles are mostly inherited together and are these genes are usually present close together on the same chromosome.

Explanation of Solution

Locus 1 is unlinked to disease gene because the father is heterozygous for CA alleles. On the contrary, one of the affected daughters is homozygous for AA alleles, and one who is not affected also has the game genotype.

Summary Introduction

e.

To draw:

A map of chromosome 4 that show the positions of the disease gene, linked SNP loci, and two crossovers and also indicate any uncertainties in these locations.

Introduction:

The process by which the offspring obtain a combination of alleles different from that of either of the parents is known as recombination.

Explanation of Solution

Pictorial representation: Fig. 1 represents the genetic map of chromosome 4 that indicates the location of the disease gene, linked SNP loci, and two crossovers. Here, A, G, T, and C indicate the SNPs (single nucleotide polymorphisms) at their respective position. The asterisk superscript indicates the genotype of disease alleles.

Fig 1. A map of chromosome 4

During meiosis, the recombination occurred at locus 8 between alleles G and T in the father. As a result of recombination, one of the sons inherited recombinant allele. Though the son is homozygous for TT allele, the son became affected due to recombination.

Summary Introduction

f.

To draw:

The position and arrangement of all alleles of all genes that are on two chromosomes in the father’s diploid genome.

Introduction:

The term diploid denotes the cells carrying two matching sets of chromosomes and is symbolized as 2x.

Explanation of Solution

Pictorial representation: Fig. 2 represents the position and arrangement of alleles on the chromosomes in the father’s diploid genome.

Fig 2. Location and arrangement of alleles

Here, A, G, C, and T denotes the single nucleotide polymorphisms and color variations indicate two sister chromatids of a diploid genome.