Overview: Genetic Mapping

Basic Principles

Genetic Mapping in Experimental Organisms

Genetic Mapping in Humans

Genes, RFLPs, SNPsMeiosis, Independent Assortment, Linkage and Crossing Over

Two- and Three-point crossesComplementation Analysis

Pedigree Analysis

Function of Human Genes

Fig. 20-13Pg. 497

Genetic Map of Drosophila

Fig. 5-14

Fig. 2-8

Gametes(haploid cells)

Crossing Over Occurs Between DNA of Homologous Chromosomes

Paternal

Maternal

PairedHomologousChromosomes

A

A

a

a

b

b

B

BaB

Ab

Pairing of Homologous Chromosomes

P

M

Fig. 2-13, 2-14

Crossing Over Occurs Between DNA of Homologous Chromosomes

Paternal

Maternal

PairedHomologousChromosomes

A

A

a

a

b

b

B

BaB

Ab

Drosophila melanogaster (Fruit Fly)

Drosophila melanogaster (Fruit Fly)

Phenotypes• eye color• body color• wing shape• antenna length• bristle pattern

Gene NameRecessive Allele

Dominant Allele (WT)

Curled Wings

Sepia Eyes sese+

Striped Body

Javelin Bristles

cucu+

jvjv+

srsr+

Double Crossover (DCO)

PairedHomologousChromosomes

Paternal

Maternal

DCO Products

February 2007

1168 Family Pedigrees with at least two ASD individuals

Neurexin Proteins

Pedigree for Inheritance of Blood Type and Nail-Patella Syndrome

GelElectrophoresis

I

II

Pedigree for Inheritance of ASD and a DNA Marker

M LASD

~ 2 cM

orf1 orf2 orf3 orf4

~ 500,000 bp

Band11q13

Chromosome 11

Population Genetics (Chapter 25)

Mendelian Genetics Applied to Populations

The Hardy-Weinberg Equation (p2 + 2pq + q2)

Test populations for microevolutionEstimate frequency of carriers for recessive genetic disordersAssess effect of natural selection and mutation on microevolutionAssess effect of inbreedingDNA Profiling (“DNA fingerprinting”)

HIV-1 Structure

(Gp120)

HIV Infection Pathway

Protein encodedby CCR5-1 allele(CCR5-1 / CCR5-1 or CCR5-1 / CCR5-∆32)

HIV-1

Gp120

Cytosol

Extra-cellularSpace

Membrane

CCR5

CD4

CCR5 RFLP

CCR5-1

CCR5-∆32

CCR5 Genotype Analysis

Fig. 25-3

CCR5-∆32 Allele Frequency

Fig. 25-4

Assumptions of the Hardy-Weinberg Equation

1. Individuals of all genotypes have equal rates of survival and reproductive success (no selection).

2. No new alleles are created or converted from one allele toanother by mutation.

3. Individuals do not migrate into or out of the population(no gene flow).

4. The population is infinitely large (no genetic drift).

5. Individuals in the population mate randomly (no inbreeding)

Page 619-620

Fig. 25-7

Effect of Selection on Allele Frequency

Fig. 25-8

Changes in CCR5-∆32 Allele Frequency

Fibroblast Growth Factor 3 (FGFR3) Receptor

840 amino acids

2520 bp ORF

FGFR3 Signal Transduction Pathways

Fibroblast Growth Factor 3 (FGFR3) Receptor

GA

C(Gly to Arg)

DELAYED LYSOSOMAL DEGREDATION

Homozygosity as a Function of Inbreeding

GTCTAG GTCTAG GTCTAG GTCTAG CAGATC CAGATC CAGATC CAGATC

Tandem Repeat Locus

(a.k.a VNTR, STR, Microsatellite)

VNTR-DVNTR-CVNTR-B VNTR-E VNTR-FVNTR-A

Chromosome 7

VNTR-DVNTR-CVNTR-B VNTR-E VNTR-FVNTR-A

7M

7P

GTCTAG GTCTAG GTCTAGCAGATC CAGATC CAGATC

GTCTAG GTCTAG GTCTAG GTCTAG CAGATC CAGATC CAGATC CAGATC

7M

7P

Fig. 22-27

RFLP Analysis of VNTR Loci