Linkage and Chromosome mapping in Eukaryotes Linked genes segregate together Chromosomes are the unit of transmission Many unit factors of inheritance are linked on each chromosome and are transmitted together there are more unt factors than chromosomes Due to crossing over during first meiotic prophase different alleles of these genes are reshuffled when the chromosomes are synapsed When there is no crossover there is complete linkage of the alleles on each homolog rare event When crossover does occur then the new combinations of alleles are produced recombinant or crossover gametes Independent assortment 2 genes on 2 different homologous pairs of chromosomes genes on different chromosomes are NOT linked together and assort independently during meiosis 50 chance of an allele of a gene on one chromosome being inherited with an allele of a second gene on another chromosome Linkage Two genes on a single pair of homologs no exchange occurs when there is no crossover there is complete linkage of the alleles on each homolog rare event two genes on a single pair of homologs exchange occurs between two nonsister chromatids when crossover does occur then new combinations of alleles are produced recombinant or crossover gametes Linkage ratios distance between genes on a chromosome is directly proportional to recombination frequency further apart than greater the frequency of recombination if 50 recombination occurs same as if on different chromosomes complete linkage as in some of Mendel s experiments Cross of fruitfly traits are eye color and wing veins ex P1 bw hv bw hv X bw hv bw hv brown thin F1 bw hv bw hv all red thin red heavy Results of a cross involving two genes located on the same chromosome where complete linkage is demonstrated Frequency of crossing over used to map distance between genes Morgan and Sturtevant 1911 observed unusual phenotypic ratios when crossing individuals with two X linked genes ex Female y w y w F1 Female X Male y w X Male y w y w y w observed 98 7 parental types in F2 generation but 1 3 non parental types Using other genes that were further apart on X chr found 62 8 parental types and 37 2 non parental types Morgan proposed chiasmata represent points of genetic exchange between chromosomes Linkage Mapping Sturtevant realized that Morgan s observations could be used to map the order of genes on chromosomes and the relative distance between them Ex mapped three loci based on crossover frequencies yellow white white miniature yellow miniature 0 5 34 5 35 4 0 5 34 5 y w m O 35 4 Single crossovers SCO Crossover must be between alleles of genes in order to be detected phenotypically Exchange Segments of two nonsister chromatids are exchanged Gametes but the linkage between the A and B alleles and between the a and b alleles is unchanged Exchange segments of two nonsister chromatids are exchanged Gametes and alleles have recombined in two of the four gametes because crossover occurs between only two members of a tetrad then one never sees more than 50 recombinants in the progeny When 50 recombination occurs then all 4 gametes are formed with equal proportions this is the same as if the genes were located on separate chromosomes Genetic mapping using multiple crossovers Consequence of double exchanged occurring between 2 nonsister chromatids is that it is the product of probabilities of individual crossovers therefore large numbers of progeny are required to detect this event Genetic Mapping three criteria for mapping 1 heterozygosity at all loci being mapped 2 all genotypes must be detectable by phenotype 3 large enough of progeny to detect all crossover classes In determining gene order 1 take one of three options and determine order of genes for 2 see if a double crossover event will give rise to any of the single crossover events observed phenotypes 3 if this does not work try one of the other 2 gene orders Determining the gene order 1 assume three possible orders and determine arrangement of alleles along each homolog of heterozygous parent 2 will a DCO occurring within that arrangement produce the 3 if that order does not work try another order there is only observed DCO phenotypes one correct answer Chromosome mapping using DNA markers and annotated computer databases linkage mapping is not useful in human where there are not a large number of progeny in any cross DNA based techniques have facilitated new ways of mapping genes in humans and similar organisms DNA markers various types SNPs RFLPs and microsatellites are short sequences whose location on a chromosome is known these serve and landmarks for mapping purposes cystic fibrosis gene was one of the first genes Other aspects of genetic exchange mapped in this way are the chiasmata observed during meiosis the sites of homologous recombination Barbara McClintock and Harriet Creighton could observe this in corn by using chromosomes with cytological markers ex a translocation at one end of a chromosome and a densely stained know region at the other looking at the offspring of the cross set up they could find the translocation and know it had become separate on different chromosomes Sister chromatid exchanges Crossover exchange between sister chromatids during mitosis can occur observed by staining with bromodeoxyuridine BUdR a thymidine analog that fluoresces Observed harlequin pattern staining is evidence that SCE has occured frequency in bloom syndrome which leads to retardation of growth sensitivity to light predisposition to cancer immune deficiency and abnormal behaviour Did Gregor Mendel Encounter Linkage Since some of the genes that Mendel studied are on the same chromosomes he might have encountered linkage however they are far apart and he does not appear to have followed them together so he may have not observed linkage or maybe he chose not to record it