Genetic linkage

Genetic linkage

It ia functionality of genes to their location on chromosomes.

Overview

Neighboring genes on the chromosome have a tendency to stick together when passed on to offsprings.Therefore, if some disease is often passed to offsprings along with specific marker-genes , then it can be concluded that the gene(s) which are responsible for the disease are located close on the chromosome to these markers.

Basic Concepts

• Locus• Allele• Genotype• Phenotype

Basic Concepts

• Locus

It is specific location of a gene or DNA sequence on a chromosome.

Basic Concepts

• Allele

A variant of the DNA sequence at a given locus is called an allele

Basic Concepts

• Genotype

The genotype is the genetic makeup of a cell, an organism, or an individual (i.e. the specific allele makeup of the individual) usually with reference to a specific character under consideration

Basic Concepts

• PhenotypeA phenotype is an

organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior (such as a bird's nest

Linkage

The further apart two genes on the same chromosome are, the more it is likely that a recombination between them will occur.

Two genes are called linked if the recombination fraction between them is small (< 50% chance)

Linkage related Concepts

• Interference -A crossover in one region usually decreases the

probability of a crossover in an adjacent region.

OR

The occurrence of one crossing over interferes with the coincident occurrence of another crossing over in the same pair of chromsomes,

Linkage related Concepts

• CentiMorgan (cM) -• 1 cM is the distance between genes for which the recombination

frequency is 1%.• One centimorgan corresponds to about 1 million base pairs in humans on

average. • Plasmodium falciparum has an average recombination distance of ~15 kb

per centimorgan: markers separated by 15 kb of DNA (15,000 nucleotides) have an expected rate of chromosomal crossovers of 0.01 per generation

Linkage related Concepts

• Crossing Over -Sometimes in meiosis, homologous chromosomes exchange parts in a

process called crossing-over or recombination.

Linkage related Concepts

• Recombination FractionThe probability for a recombination between two genes

is a monotone, non-linear function of the physical distance between their loci on the chromosome.

Linkage) No(5.0)ionRecombinat(0)Linkage( P

Linkage related Concepts

•Lod Score - a method to calculate linkage distances (to determine the distance between genes).

•Positive LOD scores favor the presence of linkage.•Negative LOD scores indicate that linkage is less likely.

Linkage related Concepts

•Lod Score -

•Establish a pedigree

•Make a number of estimates of recombination frequency

•Calculate a LOD score for each estimate

•The estimate with the highest LOD score will be considered the best

estimate

Linkage related Concepts

•Recombination frequency (θ) It is the frequency with which a single chromosomal crossover will take place between two genes during meiosis.

When two genes are located on the same chromosome, the chance of a crossover producing recombination between the genes is related to the distance between the two genes. Thus, the use of recombination frequencies has been used to develop linkage maps or genetic maps.

Linkage related Concepts

•Pedigree chart -It is a diagram that shows the occurrence and appearance or phenotypes of a particular gene or organism and its ancestors from one generation to the next, most commonly humans, show dogs, and race horses. The word pedigree is a corruption of the French "pied de grue" or crane's foot, because the typical lines and split lines (each split leading to different offspring of the one parent line) resemble the thin leg and foot of a crane

Linkage related Concepts

Pied De Grue Or

Crane's Foot

Linkage related Concepts

Pied De Grue Or

Crane's Foot

Linkage related Concepts

• Linkage map

A genetic map of a species or experimental population that shows the position of its known genes or genetic markers relative to each other in terms of recombination frequency, rather than as specific physical distance along each chromosome. Linkage mapping is critical for identifying the location of genes that cause genetic diseases.

Linkage related Concepts

• Meiosis Indicators If the allele from the 'first' copy of the parental chromosome is

transmitted, a '0' might be assigned to that meiosis. If the allele from the 'second' copy of the parental chromosome is transmitted, a '1' would be assigned to that meiosis. The two alleles in the parent came, one each, from two grandparents. These indicators are then used to determine identical-by-descent (IBD) states or inheritance states, which are in turn used to identify genes responsible for diseases and phenotypes.

With very large pedigrees or with very dense genetic marker data, such as from whole-genome sequencing, it is possible to precisely locate and quantify

Research Scope

– It’s impossible to make controlled crosses in humans.

– Human progenies are rather small.– The human genome is immense. The

distances between genes are large on average.

Possible Solutions

• Make general assumptions:Hardy-Weinberg Equilibrium :

Assumes certain probability for a certain individual to have a certain genotype.

Linkage Equilibrium :

Assumes two alleles at different loci are independent of each other.

• Incorporate those assumptions into possible solutions:

Elston-Stewart method.

Lander-Green method.

Elston-Stewart Method

• The Elston–Stewart algorithm is an algorithm for computing the liklehood of observed genotype data given a pedigree. It is due to Robert Elston and John Stewart. It can handle relatively large pedigrees providing they are (almost) outbred. Its computation time is exponential in the number of markers. It is used in the analysis of genetic linkage.

Lander-Green method

• The Lander–Green algorithm is an algorithm, due to Eric Lander and Philip Green for computing the liklehood of observed genotype data given a pedifgree. It is appropriate for relatively small pedigrees and a large number of markers. It is used in the analysis of genetic linkage.

SuperLink

• Combines the covered approaches in one unified program.

• Has other built-in abilities that increase its computations efficiency.

• Claimed to be more capable and faster than other related programs (by its own makers).

The End