1. Linkage, Recombination, and Eukaryotic Gene Mapping
Benjamin A. Pierce
GENETICS
A Conceptual Approach
SIXTH EDITION
CHAPTER 7
Linkage, Recombination, and Eukaryotic Gene Mapping
© 2017 W. H. Freeman and Company

2. Pattern baldness is a hereditary trait
Pattern baldness is a hereditary trait. Recent research demonstrated that a gene for pattern baldness is linked to genetic markers located on the X chromosome, leading to the discovery that pattern baldness is influenced by variation in the androgen-receptor gene. The trait is seen in three generations of the Adams family: John Adams (a), John Quincy Adams (b), and Charles Francis Adams (c).

3. Pattern baldness is a hereditary trait
Pattern baldness is a hereditary trait. Recent research demonstrated that a gene for pattern baldness is linked to genetic markers located on the X chromosome, leading to the discovery that pattern baldness is influenced by variation in the androgen-receptor gene. The trait is seen in three generations of the Adams family: John Adams (a), John Quincy Adams (b), and Charles Francis Adams (c).

4. 7.1 Linked Genes Do Not Assort Independently
Principle of segregation: Alleles separate during meiosis.
Independent assortment: Alleles at one locus sort independently from alleles at another locus.
Recombination: Alleles sort into new combinations.

5. 7.1 Recombination is the sorting of alleles into new combinations.

6. 7.2 Linked Genes Segregate Together and Crossing Over Produces Recombination Between Them
Notation for crosses with linkage
Complete linkage leads to nonrecombinant gametes and nonrecombinant progeny
Crossing over with linked genes leads to recombinant gametes and recombinant progeny

7. 7.2 Nonindependent assortment of flower color and pollen shape in sweet peas.

8. So what ratio do we get?

9. 7.3 Crossing over leads to recombination; if crossing over occurs between two normally linked loci, they will sort independently.

10. 7.4 Testcrosses will demonstrate whether or not two gene loci are normally linked.

11. 7.5 Single crossover: half nonrecombinant gametes, half recombinant gametes.

12. Concept Check 1
For single crossovers, the frequency of recombinant gametes is half the frequency of crossing over because
a. a testcross between a homozygote and heterozygote produces ½ heterozygous and ½ homozygous progeny.
b. the frequency of recombination is always 50%.
c. each crossover takes place between only two of the four chromatids of a homologous pair.
d. crossovers occur in about 50% of meiosis.

13. Concept Check 1
For single crossovers, the frequency of recombinant gametes is half the frequency of crossing over because
a. a testcross between a homozygote and heterozygote produces ½ heterozygous and ½ homozygous progeny.
b. the frequency of recombination is always 50%.
c. each crossover takes place between only two of the four chromatids of a homologous pair.
d. crossovers occur in about 50% of meiosis.

14. Calculating recombination frequency
7.2 Linked Genes Segregate Together and Crossing Over Produces Recombination Between Them
Calculating recombination frequency
Recombination frequency = (Number of recombinant progeny/Total number of progeny) x 100%
Coupling and repulsion configuration of linked genes
Coupling (cis configuration): wild-type alleles are found on one chromosome; mutant alleles are found on the other chromosome.

15. 7.6 Crossing over between linked genes produces nonrecombinant and recombinant offspring. In this testcross, genes are linked and there is some crossing over.

16. 7.2 Linked Genes Segregate Together and Crossing Over Produces Recombination Between Them
Coupling and repulsion configuration of linked genes
Coupling (cis configuration): One chromosome contains both wild-type alleles, one chromosome contains both mutant alleles.
Repulsion (trans configuration): Wild-type allele and mutant allele are found on the same chromosome.
Testing for independent assortment
Figs. 7.9 and 7.10

17. 7.7 The arrangement (coupling or repulsion) of linked genes on a chromosome affects the results of a testcross. Linked loci in the Australian blowfly, Lucilia cuprina, determine the color of the thorax and that of the puparium.

18. TABLE 7.1
Results of a testcross (Aa Bb X aa bb) with complete linkage, independent assortment, and linkage with some crossing over
Situation
Progeny of Testcross
Independent assortment
Aa Bb (nonrecombinant)
aa bb (nonrecombinant)
Aa bb (recombinant)
aa Bb (recombinant)
25%
Complete linkage (genes in coupling)
50%
Linkage with some crossing over (genes in coupling)
More than 50%
Less than 50%

19. 7.9 Recombination frequency allows us to predict expected offspring for a cross with linked genes.

20. 7.10 Chi-square analysis: test for independence; determines if two genes are sorting independently.

21. Concept Check 2
The following testcross produces the progeny shown: AaBb x aabb 
10 AaBb, 40 aaBb, 40 aaBb, and 10 aabb.
What is the percent recombination between the A and B loci? Were the genes in the AaBb parent in coupling or repulsion?

22. Concept Check 2
The following testcross produces the progeny shown: AaBb x aabb 
10 AaBb, 40 aaBb, 40 aaBb, and 10 aabb.
What is the percent recombination between the A and B loci? Were the genes in the AaBb parent in coupling or repulsion?
Percent recombination: 20%; genes in AaBb parent are in repulsion.

23. 7.2 Linked Genes Segregate Together and Crossing Over Produces Recombination Between Them
Gene mapping with recombination frequencies:
Genetics maps are determined by recombinant frequency.
Map unit and centiMorgans
Constructing a genetic map with two-point testcrosses
Fig. 7.11

24. 7.11 A two-strand double crossover between two linked genes produces only nonrecombinant gametes.

25. Three Types of Crossovers with Three Linked Loci
7.12 Three types of crossovers can take place among three linked loci.

26. 7.3 A Three-Point Testcross Can Be Used to Map Three Linked Genes
Constructing a genetic map with the three-point testcross
Fig. 7.13
Determining the gene order
Determining the location of crossovers
Fig. 7.14

27. 7.13 The results of a three-point testcross can be used to map linked genes. In this three-point testcross of Drosophila melanogaster, the recessive mutations scarlet eyes (st), ebony body color (e), and spineless bristles (ss) are at three linked loci. The order of the loci has been designated arbitrarily, as has the sex of the progeny flies.

28. Steps in determining gene order in a three-point cross
TABLE 7.2
Steps in determining gene order in a three-point cross
1. Identify the nonrecombinant progeny (two most numerous phenotypes).
2. Identify the double-crossover progeny (two least numerous phenotypes).
3. Compare the phenotypes of double-crossover progeny with the phenotypes of nonrecombinant progeny. They should be alike in two characteristics and differ in one.
4. The characteristic that differs between the double crossover and the nonrecombinant progeny is encoded by the middle gene.

29. Concept Check 3
A three-point testcross is carried out between three linked genes. The resulting nonrecombinant progeny are s+r+c+ and s r c, and the double-crossover progeny are s r c+ and s+r+c. Which is the middle locus?

30. Concept Check 3
A three-point testcross is carried out between three linked genes. The resulting nonrecombinant progeny are s+r+c+ and s r c, and the double-crossover progeny are s r c+ and s+r+c. Which is the middle locus?
C locus

31. 7.14 Writing the results of a three-point testcross with the loci in the correct order allows the locations of crossovers to be determined. These results are from the testcross illustrated in Figure 7.14, with the loci shown in the correct order. The location of a crossover is indicated by a slash (/). The sex of the progeny flies has been designated arbitrarily.

32. 7.15 Drosophila melanogaster has four linkage groups corresponding to its four pairs of chromosomes. These genes were mapped using recombination frequencies. Distances between genes within a linkage group are in map units. Note that the small chromosome 4 never undergoes recombination.

33. 7.3 A Three-Point Testcross Can Be Used to Map Three Linked Genes
Calculating the recombination frequencies
Sum of all single and double crossovers/Total progeny
Interference and coefficient of coincidence
Coefficient of coincidence = Number of observed double crossovers/Number of expected double crossovers
Interference = 1n – Coefficient of coincidence
Effect of multiple crossovers (Fig. 7.16)
Mapping human genes (Fig. 7.18)

34. 7.16 Effects of two-, three-, and four-strand double crossovers on recombination between two genes.

35. 7.17 Recombination rates underestimate the true physical distance between genes at higher map distances.

36. 7.18 Linkage between ABO blood types and nail–patella syndrome was established by examining families in whom both traits segregate. The pedigree shown here is for one such family. The ABO blood type is indicated in each circle or square. The genotype, inferred from phenotype, is given below each circle or square.

37. Mapping with molecular markers
Mapping Techniques
Mapping with molecular markers
RFLPs
More to come in Chapters 19 and 20
Genomewide association studies
Associations within populations
Haplotype
Linkage disequilibrium

38. 7.19 Genomewide association studies are based on the nonrandom association of a mutation (D−) that produces a trait with closely linked genes that constitute a haplotype.

39. Somatic-cell hybridization Deletion mapping
7.4 Physical-Mapping Methods Are Used to Determine the Physical Positions of Genes on Particular Chromosomes
Somatic-cell hybridization
Deletion mapping
Physical mapping through molecular analysis
In situ hybridization

40. 7.20 Somatic-cell hybridization can be used to determine which chromosome contains a gene of interest.

41. 7.21 Somatic-cell hybridization is used to assign a gene to a particular human chromosome.

42. 7.22 Deletion mapping can be used to determine the chromosomal location of a gene. An individual homozygous for a recessive mutation in the gene of interest (aa) is crossed with an individual heterozygous for a deletion.

43. 7.23 In situ hybridization is another technique for determining the chromosomal location of a gene.

44. 7.5 Recombination Rates Exhibit Extensive Variation
Levels of recombination vary widely
Among species
Among chromosomes of a single species
Between males and females
Recombination hotspots