Chapter 5 Genetics

Genetic Linkage and Mapping in Eukaryotes

Thomas Hunt Morgan's Contributions

• Nobel Prize winner for establishing the chromosome theory of inheritance.

• Identified and explained genetic linkage and recombination.

• Applied these concepts to genetic mapping.

5.1 Linked Genes Do Not Sort Independently

• Syntenic Genes: Genes located on the same chromosome.

• Linked Genes: Syntenic genes that are close together and their alleles cannot sort independently.

• Genetic linkage quantifies the distance between genes for mapping on chromosomes.

Recombination and Syntenic Genes

• Crossing Over: Alleles of syntenic genes can be reshuffled.

• Parental Chromosomes: Homologs that do not reshuffle alleles.

• Genetic linkage mapping shows gene positions through allele combination frequencies.

Independent Assortment of Syntenic Genes

• Genes far apart on a chromosome can assort independently.

• Closer Syntenic Genes: Tend to segregate together.

• Crossing over happens during prophase of meiosis, which influences gene segregation.

Observations About Genetic Linkage

• Linked genes are syntenic and located close to one another.

• More gametes show parental combinations than nonparental due to genetic linkage.

• Crossing over is less likely between closely linked genes.

Detecting Genetic Linkage

• Recognized by comparing observed frequencies of gamete genotypes with expected frequencies from independent assortment.

• Linked genes show higher incidence of parental allele combinations than predicted.

Gametes of Dihybrids of Unlinked and Linked Genes

• Dihybrid AaBb undergoes independent assortment for unlinked genes, producing four gamete combinations equally.

• For linked genes (e.g., A and B), parental combinations occur >50%; nonparental combinations occur <50%.

Complete Genetic Linkage

• Observed when no crossing over occurs; only parental gametes form.

• Example: Drosophila males show complete linkage with no crossing over.

Incomplete Genetic Linkage

• More common than complete linkage; produces mixed parental and nonparental gametes.

• Parental types are roughly equal in frequency to recombinant types.

5.2 Genetic Linkage Mapping Based on Recombination Frequency

• Morgan identified that linked genes yield more parental offspring and varied recombinant frequencies.

• Proximity of genes correlates with parental allele combination frequency.

The First Genetic Linkage Map

• Alfred Sturtevant, Morgan's student, developed the first genetic map using recombination frequencies.

Map Units

• Physical distances expressed in map units (m.u.), with 1% recombination equating to 1 m.u. or centiMorgan (cM).

Chi-Square Analysis of Genetic Linkage Data

• Tests for significant association by comparing observed ratios of parental to recombinant types against expected ratios.

5.3 Three-Point Test-Cross Analysis Maps Genes

• Enables efficient mapping of three linked genes simultaneously.

• Involves identifying parental, single-crossover, and double-crossover gametes.

Example Genetic Crosses and Gamete Frequencies

• Specific examples illustrate complex crossover scenarios and resulting gamete classes with variably distributed frequencies.

5.4 Factors Affecting Recombination

• Factors include species, age, environment, and sex affecting recombination frequency.

• Female fruit flies show decreased recombination rates with increased age; temperature and calcium levels also impact.

Influence of Sex on Recombination Rates

• Heterogametic sex generally has lower recombination rates.

• In fruit flies, there is no crossing over in males.

Recombination and Natural Selection

• Artificial selection often increases recombination rates; evolution is enhanced by recombination.

5.5 Human Gene Mapping Challenges

• Challenges in mapping human genes due to difficulty in controlled matings and offspring counts.

• X-linked genes were the first to map successfully using polymorphic DNA sequences as genetic markers.

Linkage Groups and Genetic Markers

• Clusters of linked syntenic genes are termed linkage groups.

• Genetic markers used include VNTRs, SNPs, and RFLPs.

Genetic Marker Types

• VNTRs: Repeats of short DNA sequences; variability among chromosomes.

• SNPs: Single base pair variations frequent in genomes; over 3 million in humans.

• RFLPs: Changes in DNA detected by restriction endonucleases that cut DNA at specific sequences.

Inheritance of Disease-Causing Genes

• Haplotype: array of SNPs on a single chromosome; linked variants passed during meiosis.

Lod Score Analysis

• A statistical method for assessing genetic linkage probability, comparing likelihoods of observed versus expected distributions of genotypes.

Genome-Wide Association Studies (GWAS)

• Identifies genes influencing traits across populations using linked markers.

• High P-values in GWAS indicate significant presence of genes associated with traits.

Interpreting Linkage Disequilibrium

• Linkage disequilibrium indicates deviations from expected genotypic frequencies; can locate contributing genes linked to diseases.

• Manhattan plots visually represent GWAS results, indicating strong associations between traits and genes.