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Linkage analysis Nasir Mehmood Roll No:117102 Linkage analysis Linkage analysis is statistical method that is used to associate functionality of genes to their location on chromosomes. 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. Linkage Analysis Linkage analysis is a method that is used in establishing the carrier status of female 'at-risk' carriers and for prenatal diagnosis. In many cases, linkage analysis has been replaced by mutational analysis but in a small number of families in whom the mutation cannot be identified, linkage analysis remains the only method for the genetic diagnosis of carriers. Two genetic loci are said to be in linkage if the alleles at these loci segregate together more often that would be expected by chance that is the two loci are so close together on the same chromosome that the chances of them separating by a crossover event (recombination) during Meiosis is small. The probability that any two alleles at two randomly selected loci with be inherited together is 0.5. If two loci are closely linked then the chances of a crossover or recombination event occurring is <0.5. The chances of recombination taking places is linked to the distance between any two loci. The recombination fraction is a measure of the genetic distance between two loci. The distance between two loci is measured in centimorgans 1 centimorgan is defined as the genetic distance between two loci with a recombination frequency of 1%. Although the centimorgan is not a measure of physical distance, it typically equates to a physical distance of one million base pairs Aim of linkage analysis The aim of linkage analysis is to identify a marker that co-segregates with the gene of interest and so can be used to track the gene within a family without actually knowing the mutation. By definition this marker must co-segregate with the gene of interest and so be present in affected family members but absent in unaffected family members. Chromosomal theory of Linkage: Linked genes are located on homologous chromosomes The linkage of genes is linear .this shows that the genes themselves are arranged in a line inside the chromosomes Genes situated closely in chromosomes posses strong linkage while the linked genes situated farther from each other show week linkage Example of linkage analysis we usually think of linkage analysis using DNA markers, other markers such as proteins can be also be used. Such a case is the gene for Glucose-6 Phosphate Dehydrogenase [G6PD] which maps to the long arm of the X-chromosome at Xq28 close to the gene for factor VIII [F8]. References //www.illumina.com/applications/detail/sn p_genotyping_and_cnv_analysis/linkage_a nalysis.ilmn /practicalhaemostasis.com/Genetics/linkage_analysi s1.htmlhttp://practicalhaemostasis.com/Genetics/linkage_analysi s1.html Genetics book by Dr.Ali Muhammad