Title Page

Objective

General Introduction

Basic Anatomy of the Mammalian Genome
 Inherited Phenotypes

Genetic Linkage

 Two loci, A and B, for which the proportion of parental gametes (1-q ) produced exceeds the proportion of recombinant gametes (q )(violation of Mendel's second law) are said to be genetically linked (1 ).

 Counting parental versus recombinant gametes requires knowledge of the linkage phase, i.e. grouping the alleles of the individual producing the gametes by parental origin.

 Genetic distance (x):

  • The recombination rate (q ) between two loci is a function of the genetic distance between the two loci (x) expressed in Morgan (x).
  • x corresponds to the average number of crossovers occurring between loci A and B per gamete and per generation.
  • The distinction between q and x result from the fact that gametes having undergone an even number of crossovers will be mistaken as non recombinant gametes.
  • Several functions relating q and x are being used, including:

Haldane's mapping function:

assumes that the frequencies of meioses with 0, 1, 2, …,n crossovers between loci A and B are distributed as a Poisson process with mean m:

as all but meioses with 0 crossovers produce 50% recombinant and 50% parental gametes (1 ):

As m = 2x,

and

 

Kosambi's mapping function:

Allows for interference (I), whereby one crossover tends to prevent other crossovers in the same region:

The amount of interference allowed in the Kosambi map function decreases as the loci get further apart, and is zero for unlinked loci:

Kosambi's mapping function is the preferred mapping function in mammals.

 The genetic distance, x, between two loci is a function of:

  • The physical distance between the two loci
  • The recombinogenic potential of the intervening sequences: the genome is characterized by recombination hot- and cold spots (1).
  • The sex of the parent: generally speaking, the recombination rate between two loci is expected to be higher in the homogametic sex than in the heterogametic sex. In some chromosome regions, however, such as subtelomeric and imprinted regions, this ratio may be inverted (1).
  • Individual variation in recombination rates.

 The total genetic map length, and therefore the average kb / cM ratio, differs between species:

 

Species

Sex-averaged map

Female map

Male Map

Human

 

 43 M

28.5 M 

Mouse

 16 M

 

 

Cattle

 29.9 M

 

 

Pig

 

 

 

 

Linkage Disequilibrium

Genetic Markers

 Map Construction

 QTL Mapping in Outbred Half-Sib Pedigrees

References