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Chapter 7 – Linkage, Recombination, and Eukaryotic Gene Mapping

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1 Chapter 7 – Linkage, Recombination, and Eukaryotic Gene Mapping

2 Genetic Principles Principle of Segregation
Diploid organisms have 2 alleles for each gene Separate during meiosis – only one gamete enters each gamete Principle of Independent Assortment 2 alleles of a gene separate independently from alleles at other loci/other genes

3 Chromosomes Chromosomes follow independent assortment IF:
Genes are located of different chromosomes BUT: If genes are on the same chromosome, they tend to travel together Linked genes – close together on the same chromosome

4 Sweet peas – dihybrid cross
P generation purple, long x red, round F1 generation – all purple,long Prediction for F2 generation – ratio of 9:3:3:1

5 Sweet pea – dihybrid cross cont
Expected F2 phenotype ratios is not observed Conclusion – genes for flower color and pollen shape must be located close together on the same chromosome Why are any recombinant progeny seen?

6 Crossing over If 2 genes are on the same chromosome, but far apart, crossing over can allow for recombination of gametes Genes very far apart on the same chromosome will always be separated by crossing over, and are not considered to be linked

7 Notation for linked genes
Horizontal lines indicate actual chromosome A_________B a b *individual heterozygous for 2 different genes where both dominant alleles are on one chromosome, and both recessive alleles are on its homologous chromosome Can be abbreviated by AB/ab

8 Testcross for linkage For determination if two genes are linked (close together on the same chromosome) or not Set-up: One individual heterozygous for both traits x individual homozygous recessive for both traits

9 Testcross for linkage cont
MmDd x mmdd If not closely linked, alleles will assort independently MmDd individual can form 4 different types of gametes 50% recombinant offspring/50% non-recombinant offspring

10 Testcross for linkage cont
MD/md x md/md If closely linked, 2 alleles will always travel together all offspring are non-recombinant

11 Testcross for linkage cont
Can be separated by crossing over Small number of recombinant progeny/chromosomes is seen

12 Crossing over Single cross over produces 50% nonrecombinant chromosomes (same configuration as parental chromosome) and 50% recombinant chromosomes (new allelic combination)

13 Recombination frequency
= number of recombinant progeny x 100 total number of progeny Values from slide #11 = 123 = 12.2% or .122 Smaller the recombination frequency = more closely linked

14 Coupling and Repulsion
For heterozygous individuals Cis configuration/coupling Both wildtype alleles are on one chromosome; both mutant alleles are on the homologous chromosome Trans configuration/repulsion Each chromosome has one wildtype allele and one mutant allele


16 Recombination Interchromosomal Intrachromosomal
Between genes on different chromosomes Independent assortment/random segregation during Metaphase/Anaphase I Produces 50% recombinant/50% non-recombinant gametes Intrachromosomal Between genes on same chromosome Crossing over during Prophase I Usually produces recombinant gametes less than 50% Unless very far apart on the same chromosome

17 Genetic mapping Relative position of different genes based on recombination rates Does NOT state actual chromosome, or position (locus) Distance measured in map units or centimorgans (cM) 1 m.u. (or cM) = 1% recombination

18 Genetic mapping example
A and B = 5 m.u. A and C = 15 m.u. B and C = 10 m.u. A and D = 8 m.u. B and D = 13 m.u. C and D = 23 m.u. Any genes with 50% recombination are either on different chromosomes, or very far apart on the same chromosome (crossing over always separates them)

19 Physical mapping Locates gene to a specific chromosome/region of chromosome Deletion mapping Chromosome deletion studies – how phenotype is affected/what genes may be missing Duchenne m.s. X linked disease – but where on X? Some affected males have small deletions – common deleted area must be where gene is located

20 Somatic cell hybridization
Fusion of 2 cell types (altered by viruses or tumor cells to allow cell lines – uninhibited growth) Somatic cells Heterokaryon – 2 distinct nuclei Eventually fuse Most chromosomes are lost (differentially from one type) Human chromosomes usually lost, only a few remain Human genes expressed in hybrid cell lines must be located on retained chromosomes deletion studies can give more specific location on chromosome


22 Molecular Analysis Fluorescence In Situ Hybridization (FISH)
Probe complementary to gene sequence will bind to DNA Gene sequence/partial sequence must be known DNA sequencing Yields base pair distance between two genes

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