4. Genetic Mapping and Linkage

Mapping Genes

Open Question
Traditional gene mapping has been applied successfully to a variety of organisms including yeast, fungi, maize, and Drosophila. However, human gene mapping has only recently shared a similar spotlight. What factors have delayed the application of traditional gene-mapping techniques in humans?
Open Question
In a certain plant, fruit is either red or yellow, and fruit shape is either oval or long. Red and oval are the dominant traits. Two plants, both heterozygous for these traits, were testcrossed, with the following results.Determine the location of the genes relative to one another and the genotypes of the two parental plants.
Open Question
Two plants in a cross were each heterozygous for two gene pairs (Ab/aB) whose loci are linked and 25 mu apart. Assuming that crossing over occurs during the formation of both male and female gametes and that the A and B alleles are dominant, determine the phenotypic ratio of their offspring.
Open Question
Neurofibromatosis 1 (NF1) is an autosomal dominant disorder inherited on human chromosome 17. Part of the analysis mapping the NF1 gene to chromosome 17 came from genetic linkage studies testing segregation of NF1 and DNA genetic markers on various chromosomes. A DNA marker with two alleles, designated 1 and 2, is linked to NF1. The pedigree below shows segregation of NF1 (darkened symbols) and gives genotypes for the DNA marker for each family member. What is the estimated recombination frequency between the NF1 gene and the DNA marker? <
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Open Question
Neurofibromatosis 1 (NF1) is an autosomal dominant disorder inherited on human chromosome 17. Part of the analysis mapping the NF1 gene to chromosome 17 came from genetic linkage studies testing segregation of NF1 and DNA genetic markers on various chromosomes. A DNA marker with two alleles, designated 1 and 2, is linked to NF1. The pedigree below shows segregation of NF1 (darkened symbols) and gives genotypes for the DNA marker for each family member.

Based on the phase of alleles on chromosomes in generation II, is there any evidence of recombination among the eight offspring in generation III? Explain. <>
Open Question
Neurofibromatosis 1 (NF1) is an autosomal dominant disorder inherited on human chromosome 17. Part of the analysis mapping the NF1 gene to chromosome 17 came from genetic linkage studies testing segregation of NF1 and DNA genetic markers on various chromosomes. A DNA marker with two alleles, designated 1 and 2, is linked to NF1. The pedigree below shows segregation of NF1 (darkened symbols) and gives genotypes for the DNA marker for each family member.

Determine the alleles for the NF1 gene and the DNA marker gene on each chromosome carried by the four family members in generation I and generation II. Use N for the dominant NF1 allele and n for the recessive allele and assume I-1 is heterozygous for the disease allele (Nn). <>
Open Question
A number of human–mouse somatic cell hybrid clones were examined for the expression of specific human genes and the presence of human chromosomes. The results are summarized in the following table. Assign each gene to the chromosome on which it is located.
Open Question
A 2006 genetic study of a large American family (Ikeda et al., 2006) identified genetic linkage between DNA markers on chromosome 11 and the gene producing the autosomal dominant neuromuscular disorder spinocerebellar ataxia type 5 (SCA5). The following lod score data are taken from the 2006 study: Theta (θ) Value 0.01 0.05 0.10 0.20 0.30 0.40SCA5 11.02 12.26 11.94 10.04 7.26 3.77 and DNA marker A SCA5 0.35. 0.94. 1.07 0.99 0.75 0.43 and DNA marker B Based on the available information, is DNA marker A linked to the gene producing SCA5? Explain your answer.
Open Question
A 2006 genetic study of a large American family (Ikeda et al., 2006) identified genetic linkage between DNA markers on chromosome 11 and the gene producing the autosomal dominant neuromuscular disorder spinocerebellar ataxia type 5 (SCA5). The following lod score data are taken from the 2006 study: Theta (θ) Value 0.01 0.05 0.10 0.20 0.30 0.40SCA5 11.02 12.26 11.94 10.04 7.26 3.77 and DNA marker A SCA5 0.35. 0.94. 1.07 0.99 0.75 0.43 and DNA marker B What is the maximum value for each set of lod scores?
Open Question
A 2006 genetic study of a large American family (Ikeda et al., 2006) identified genetic linkage between DNA markers on chromosome 11 and the gene producing the autosomal dominant neuromuscular disorder spinocerebellar ataxia type 5 (SCA5). The following lod score data are taken from the 2006 study: Theta (θ) Value 0.01 0.05 0.10 0.20 0.30 0.40SCA5 11.02 12.26 11.94 10.04 7.26 3.77 and DNA marker A SCA5 0.35. 0.94. 1.07 0.99 0.75 0.43 and DNA marker B Does either group of lod scores indicate statistically significant odds in favor of genetic linkage? Explain your answer.
Open Question
A 2006 genetic study of a large American family (Ikeda et al., 2006) identified genetic linkage between DNA markers on chromosome 11 and the gene producing the autosomal dominant neuromuscular disorder spinocerebellar ataxia type 5 (SCA5). The following lod score data are taken from the 2006 study:

Theta (θ) Value
0.01 0.05 0.10 0.20 0.30 0.40
SCA5 11.02 12.26 11.94 10.04 7.26 3.77
and
DNA
marker A

SCA5 0.35. 0.94. 1.07 0.99 0.75 0.43
and
DNA
marker B

Based on available information, is DNA marker B linked to the gene for SCA5? Explain your answer.
Open Question
A female of genotypea b c + + +produces 100 meiotic tetrads. Of these, 68 show no crossover events. Of the remaining 32, 20 show a crossover between a and b, 10 show a crossover between b and c, and 2 show a double crossover between a and b and between b and c. Of the 400 gametes produced, how many of each of the 8 different genotypes will be produced? Assuming the order a–b–c and the allele arrangement previously shown, what is the map distance between these loci?
Open Question
A genetic study of an early onset form of heart disease identifies 10 families containing members with the condition. No clear dominant or recessive pattern of inheritance is evident, but an analysis of SNP markers for five families detects a strong association with a marker on chromosome 12, and genetic linkage analysis for the marker produces a lod score of 2.2.

What next step do you recommend for this genetic analysis?
Open Question
A genetic study of an early onset form of heart disease identifies 10 families containing members with the condition. No clear dominant or recessive pattern of inheritance is evident, but an analysis of SNP markers for five families detects a strong association with a marker on chromosome 12, and genetic linkage analysis for the marker produces a lod score of 2.2.

What do the association and lod score results suggest about this genetic marker?
Open Question
In Drosophila, a female fly is heterozygous for three mutations, Bar eyes (B), miniature wings (m), and ebony body (e). Note that Bar is a dominant mutation. The fly is crossed to a male with normal eyes, miniature wings, and ebony body. The results of the cross are as follows.111 miniature 101 Bar, ebony29 wild type 31 Bar, miniature, ebony117 Bar 35 ebony26 Bar, miniature 115 miniature, ebonyInterpret the results of this cross. If you conclude that linkage is involved between any of the genes, determine the map distance(s) between them.