1. Gene Linkage and Genetic Mapping4
Gene Linkage and Genetic Mapping

2. Mendel’s Laws: Chromosomes
Homologous pairs of chromosomes: contain genes whose information is often non-identical =alleles
Different alleles of the same gene segregate at meiosis I
Alleles of different genes assort independently in gametes
Genes on the same chromosome exhibit linkage: inherited together

4. Gene Mapping
Gene mapping determines the order of genes and the relative distances between them in map units
1 map unit=1 cM (centimorgan)
Alleles of two different genes on the same chromosome are cis
Alleles of two different genes on different homologues of the same chromosome are trans

5. Gene Mapping
Gene mapping methods use recombination frequencies between alleles in order to determine the relative distances between them
Recombination frequencies between genes are inversely proportional to their distance apart
Distance measurement: 1 map unit = 1 percent recombination

7. Gene Mapping
Recombination between linked genes located on the same chromosome involves homologous crossing-over = allelic exchange between them
Recombination changes the allelic arrangement on homologous chromosomes = recombinant

9. Gene Mapping
Genes with recombination frequencies less than 50 percent are on the same chromosome (linked)
Two genes that undergo independent assortment have recombination frequency greater than 50 percent and are located on nonhomologous chromosomes or far apart on the same chromosome (unlinked)

11. Recombination
Recombination between linked genes occurs at the same frequency whether alleles are in cis or trans configuration
Recombination frequency is specific for a particular pair of genes
Recombination frequency increases with increasing distances between genes

12. Genetic Mapping
Map distance between two genes = one half the average number of crossovers in that region
Map distance=recombination frequency over short distances because all crossovers result in recombinant gametes
Genetic map = linkage map = chromosome map

13. Genetic Mapping Linkage group = all known genes on a chromosome
Physical distance does not always correlate with map distance; less recombination occurs in heterochromatin than euchromatin
Locus=physical location of a gene on chromosome

14. Gene Mapping: Crossing Over
Crossing-over between genes on homologous chromosomes changes the linkage arrangement of alleles on a single chromosome
Two exchanges between the same chromatids result in a reciprocal exchange of the alleles in the region between the cross-over points

16. Gene Mapping: Crossing Over
Cross-overs which occur outside the region between two genes will not alter their arrangement
Double cross-overs restore the original allelic arrangement
Cross-overs involving three pairs of alleles specify gene order = linear sequence of genes

18. Genetic vs. Physical Distance
Map distances based on recombination frequencies are not a direct measurement of physical distance along a chromosome
Recombination “hot spots” overestimate physical length
Low rates in heterochromatin and centromeres underestimate actual physical length

19. Gene Mapping
Mapping function: the relation between genetic map distance and the frequency of recombination
Chromosome interference: cross-overs in one region decrease the probability of second cross-over
Coefficient of coincidence=observed number of double recombinants divided by the expected number

20. Gene Mapping: Human Pedigrees
Methods of recombinant DNA technology are used to map human chromosomes and locate genes
Genes can then be cloned to determine structure and function
Human pedigrees and DNA mapping are used to identify dominant and recessive disease genes

21. Gene Maps: Restriction Endonucleases
Restriction endonucleases are used to map genes as they produce a unique set of fragments for a gene
EcoR1 cuts ds DNA at the sequence = 5’-GAATTC-3’ wherever it occurs
There are >100 restriction endonucleases in use, and each recognizes a specific sequence of DNA bases

23. Gene Maps: Restriction Enzymes
Differences in DNA sequence generate different recognition sequences and DNA cleavage sites for specific restriction enzymes
Two different genes will produce different fragment patterns when cut with the same restriction enzyme due to differences in DNA sequence

25. Gene Maps: Restriction Enzymes
Polymorphism= relatively common genetic difference in a population
Changes in DNA sequence = mutation may cause polymorphisms which alter the recognition sequences for restriction enzymes = restriction fragment length polymorphisms (RFLPs)

27. Gene Maps: Restriction Enzymes
RFLPs can map human genes
Genetic polymorphism resulting from a tandemly repeated short DNA sequence = simple tandem repeat polymorphism (STRP)
Most prevalent type of polymorphism is a single base pair difference = simple-nucleotide polymorphism (SNP)
DNA chips can detect SNPs

28. Human Gene Mapping
Human pedigrees can be analyzed for the inheritance pattern of different alleles of a gene based on differences in STRPs and SNPS
Restriction enzyme cleavage of polymorphic alleles differing RFLP pattern produces different size fragments by gel electrophoresis

30. Gene Mapping: Tetrad Analysis
In Neurospora, meiotic cell division produces four ascospores; each contains a single product of meiosis
Analysis of ascus tetrads shows recombination of unlinked genes
Tetrad analysis shows products of single and double 2, 3 and 4 strand cross-overs of linked genes

32. Tetrad Analysis
In tetrads when two pairs of alleles are segregating, 3 possible patterns of segregation:
-parental ditype (PD): two parental genotypes
-nonparental ditype (NPD): only recombinant combinations
-tetratype (TT): all four genotypes observed

34. Neurospora: Meiotic Segregation
Products of meiotic segregation can be identified by tetrad analysis
Meiosis I segregation in the absence of cross-overs produces 2 patterns for a pair of homologous chromo- somes
Meiosis II segregation after a single cross-over produces four possible patterns of spores

36. Tetrad Analysis
Unlinked genes produce parental and nonparental ditype tetrads with equal frequency
Linked genes produce parental ditypes at much higher frequency than nonparental ditype
Gene conversion = identical alleles produced by heteroduplex mismatch repair during recombination

37. Recombination: Holliday Model
Homologous recombination:
single-strand break in homologues pairing of broken strands occurs
branch migration: single strands pair with alternate homologue
nicked strands exchange places and gaps are sealed to form recombinant by Holliday junction-resolving enzyme