Ch5- Genetic Linkage and Mapping in Eukaryotes

BLANK genes do NOT sort independently

Linked

Genes located on the same chromosomes are called?

Syntenic genes

Syntenic genes so close together that their alleles cannot sort independently are called BLANK

Linked genes

BLANK can be quantified to map the positions of genes on chromosomes

Genetic linkage

Alleles of Syntenic genes can be reshuffled when crossing over occurs between Homologs to produce BLANK

Recombinant chromosomes

Homologs that do not reshuffle ales under study are called BLANK or BLANK

Parental chromosomes or non recombinant chromosomes

BLANK plots the positions of genes on chromosomes

Genetic linkage mapping

BLANK of Syntenic genes can occur if they are BLANK on a chromosomes so that recombination occurs very frequently

*Syntenic gene that are closer together will tend to segregate BLANK

Crossing over that prevent linked genes from segregating together occurs during BLANK of meiosis

Independent assortment

Far apart

Together

Prophase I

Linked genes are always BLANK and always located near one another

Genetic linkage leads to the production of significantly BLANK gametes with parental allele combinations than non parental combinations

Syntenic

More

Crossing over is BLANK likely to occur between closely linked genes than between those farther apart on a chromosome

Genetic linkage can be recognized by comparing BLANK of gamete genotypes or BLANK of phenotypes with those expected under independent assortment

If genes are BLANK parental allele combinations with be observed at a BLANK frequency than predicted by chance

Less likely

Observed frequencies, progeny

Linked, higher

Gametes of unlinked and linked genes

Complete Genetic Linkage is observed when BLANK occurs between linked genes, only BLANK gametes are formed

Some organs is exhibit complete linkage for example: BLANK males have no known crossing over (biological basis unknown)

Crossing over

Parental

Drosophila

Incomplete Genetic Linkage is BLACK than complete linkage, in this case a BLANK of parental and non parental gametes is produced

The two parental types are approximately BLANK in frequency as are the two recombinant types

The proportion of parental to recombinant chromosomes or gametes varies between different pairs of genes

Much more common

Mixture

Equal

Complete VS incomplete genetic linkage

Recombination frequency expressed as r is calculated as

Recombination frequency is likely a BLANK of the physical distance between BLANK genes

*crossing over occurs at a higher rate between genes that are BLANK apart

*at a lower rate between genes BLANK together

*linked genes with higher recombination frequencies are BLANK distant from one another than genes with lower frequencies

Reflection, two

*farther apart

*closer together

*more

Detecting Linkage- Test Cross Analysis

Morgan realized that linkage of BLANK in drosophila could be interpreted using a BLANK

• in a test cross the BLANK parent contributes only recessive alleles

• thus the allies contributed by just the BLANK parent can be examined

Autosomal genes, two-point test-cross analysis

Homozygous recessive

Dihybrid

Crosses with vg and pr

Morgan crossed flies with purple eyes and vestigial (short) wings to wild type and obtained BLANK

The F1 females were than crossed to males that had purple eyes and vestigial wings

The alleles in the female gametes in this cross determined the BLANK in each of the progeny

Offspring produced BLANK fit the 1:1:1:1 expected ratio

Wild-type F1

Phenotype

Did not fit

Important Conclusions

BLANK is a physical relationship among BLANK located near one another on a chromosomes

Recombination occurs among linked genes less than BLANK of the time, and greater than BLANK of the gametes contain parental allele combinations

Recombination frequency varies among linked genes in BLANK to the BLANK between them

Genetic Linkage, genes

50%, 50%

Proportion, distance

Cytological Evidence of Recombination

Creighton and McClintock studied recombination between copies of chromosomes 9 in corn using two genes BLANK and BLANK, and two structural differences between the Homologs

*the chromosomes with the cl and Wx alleles was BLANK

*the chromosome with the CL and wx allies had a darkly staining BLANK at one end and a garment of chromosome BLANK at the other end

cl and wx

Normal

Knob

8

Cytological evidence of recombination

Creighton and McClintock obtained Cytological evidence that recombination between the genes was accompanied by BLANK between the Homologs

*a recombination chromosome with the cl and wx alleles also had the fragment of chromosome BLANK on it

*the recombinant chromosome with the Cl and Wx alleles also had the darkly staining BLANK on it

Creighton and McClintock as as stern studying drosophila, showed that crossover is accomplished by BLANK and BLANK in plants and animals

Physical exchange

8

Knob

Chromosome breakage and rejoining

BLANK was the first to demonstrate that genes are on chromosomes

His student BLANK used the results of several experiments to create a BLANK for the five X-linked genes in drosophila

Morgan

Alfred Sturtevant

Create a genetic map for five

BLANK between two genes can be converted into units of BLANK or BLANK

*this unit is also called a BLANK

*by convention 1% recombination = 1 m.u. Or 1cM

Recombination frequencies

Physical distance, map units (m.u.)

centiMorgan (cM)

Recombination is dominated by BLANK

detailed assessment of recombination in human, mouse, yeast genomes reveals recombination BLANK or BLANK within each genome

Hotspots

Recombination cold spots

Hotspots and cold spots may lead to placement of genes BLANK or BLANK respectively on the recombination map than on the physical map

Hotspots and cold-spots may be due to the BLANK of DNA in those regions to initiate crossing over (ex cold spots between genes separated by a centromere)

Farther apart or closer together

Feasibility

Recent studies indicate that recombination occurs primarily at specific BLANK

*BLANK research by BLANK indicates that recombination hotspots are distributed unevenly and span relatively short segments of DNA

Similar results in mammalian genomes

Hotspots

*drosophila, Nadia Singh

Mapping of human genes has been more challenging than many other organisms where controlled matings are possible and larger numbers of offspring are produced

In the mid BLANK methods to identify BLANK and improved gene-mapping software facilitated human genome mapping efforts

These polymorphic DNA sequences are called BLANK

Mid-1980s, polymorphic DNA sequences

Genetic markers

The availability of large numbers of DNA markers on each chromosomes led to the identification of BLANK

Linkage groups

Linkage groups are?

Clusters of syntenic genes that are linked to one another

What assigns the linkage group to a nearby chromosomal location?

Linkage between a genetic marker with a known chromosomal location and a member of a linkage group

Different variants of DNA sequence constitute the genetic markers used to study locations of genes

Genetic Markers are typically in BLANK regions of the genome

These markers includes three things?

Noncoding regions

1- variable number tandem repeats (VNTRs)

2- single nucleotide polymorphisms (SNPSs)

3- restriction fragment length polymorphisms (RFLPs)

BLANK are short DNA sequences (? Bp)

• these sequences repeat end-to-end in a chromosomal region

• Different chromosomes can carry different repeat numbers of the sequences

• Repeat length can varry

VNTRs 3-20 bp

BLANK (? Bp)

• more commonly used markers than BLANK

• These involve variants with BLANK is substituted by another base pair, typically in a non coding region

• There are approx BLANK SNPs in the human genome

SNPs 1 bp

VNTRs

One base pair

3.3 million

BLANK are changes in DNA sequence that are detected using DNA-cutting enzymes called BLANK (BLANK)

RRLPs

Restriction endonucleases (restriction enzymes)

Restriction enzymes recognizes and BLANK specific sequences of DNA

Pieces of DNA resulting from restriction enzyme cutting are called BLANK

Cut

Restriction fragments

The specific array of SNPs in a small region on a single chromosome is called a BLANK

These SNPs are BLANK variants and will tend to be BLANK during meiosis

Haplotypes may differ between the members of chromosomes pair- maternal and paternal chromosomes may have different haplotypes in a single individual

Haplotype

Closely linked, passed on together

A first obstacle to mapping human genes is the difficulty of determine BLANK

Allelic phase

Define allelic phase

*when a disease causing allele is seen to segregate along with a known genetic marker BLANK can be determined

The arrangement of alleles of linked genes on parental chromosomes

Allelic phase

A statistical method allows geneticists to calculate the overall probability of genetic linkage between genes or trait and a marker

Compares the likelihood of obtaining the genotypes and phenotypes observed in the pedigree BLANK two genes are linked BLANK the likelihood if they are unlinked

The BLANK gives the BLANK score

If, verses

Logarithm of the odds ratio gives the LOD score

Interpreting LOD scores

A LOD of BLANK or higher significant evidence in favor of linkage at the theta values

A LOD score of less than BLANK significant evidence against genetic linkage

LOD scores between these two values are BLANK

The BLANK values indicated the recombination frequency most likely to be correct

3.0

-2.0

Inconclusive

Z max

Problem

Problem

Problem

The genetic mapping approach involves a series of linked markers along a chromosomes to form a genetic map of the chromosome (one step at a time) - contrast to BLANK

GWAS

BLANK detects and locates genes that influences traits BLANK of multiple genes

*the influential genes may be BLANK throughout the genome

*identifies where in the genome the BLANK influencing a single trait are located

Genome-wide association studies (GWAS)

As a group

Genes

GWAS looks for BLANK between traits and groups of alleles in BLANK

*BLANK are the typical genetic markers for GWAS due to their frequent distribution in most Genomes

*GWAS uses closely linked BLANK in haplotype groups with known chromsome locations

Associations, populations

SNPs

GWAS Results are represented in the BLANK

Manhattan plot

A Manhattan plot indicates?

The locations of genes contributing to the development of traits and conditions

The BLANK the green bar on the plot the stronger the association between a potential contributing genes and a chromosomal location

Higher

BLANK distribution of alleles for linked genes (or linked gene and marker)

When frequencies of haplotypes in a population deviate significantly from what is expected it is called BLANK

Reflects the BLANK relationship between alleles of closely linked genes

Means the gene we are studying is closely associate to the BLANK

Can only be separated by BLANK which are random and infrequent

Nonrandom

Linkage disequilibrium

Non-random

SNP haplotype

cross overs

If linkage disequilibrium is found in a SNP haplotype then what?

Activities associated with identifies genes are then identified to determine if their action may contribute to the condition

For example: the BLANK gene was suggested to be associate with BLANk based on GWAS results (more recently named BLANK gene)

Further study indicated that BLANK variant alleles associated with CD increased inflammatory response of intestinal tissue therapy contributing to CD development

All genes located in the chromosomes region must be identified

CARD15, Crohn’s Disease (CD), NOD2 gene

CARD15 gene