feb_14_2011_lecture

feb_14_2011_lecture - Mapping Genes by Linkage &...

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1 Mapping Genes by Linkage & Association ± Once we have evidence that a disease is genetic, we can use genetic, not functional, information to localize the responsible gene or genes ± The two common methods of this are linkage and association analysis ± For this class, we will focus on association analysis ± A brief introduction to linkage will be helpful Linkage Analysis ± Within families, compare the presence or absence of an illness with the pattern of inheritance of different chromosomal regions ± Linkage of the disease to a particular chromosomal region suggests that a gene involved in that illness resides in that chromosomal region
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2 Linkage Analysis DNA Marker Sequence Study Participant Collect Cells from Participant Extract DNA from Cells Identify Region of Interest Linkage Analysis DNA regions that are shared by individuals with the illness may contain a gene involved in susceptibility By following the inheritance of marker sequences, we can determine which regions of which chromosomes sibling have inherited in common
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3 Linkage Analysis Every time the red fragment is passed to a child with the illness or the blue fragment to a child without the illness add evidence for involvement of this region Localizing Power of Linkage Linkage analysis can quickly narrow the location of a gene to ~10 Mb Finer localization with linkage analysis becomes very difficult
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4 Localizing Disease Genes Other mapping methods are needed to further localize a disease- causing gene Linkage Disequilibrium ± Loci that are very tightly linked will be unlikely to show recombination, even over many generations ± Specific alleles at such neighboring loci will tend to be inherited together, and so exist together in the population ± Such loci are said to be in linkage disequilibrium with each other ± When specific allele travel together, it may also be called allelic association
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5 Association Analysis ± Like linkage analysis, association analysis evaluates the correlation between the presence of a given DNA sequence and an illness ± Unlike linkage, association analysis can be
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This note was uploaded on 04/04/2011 for the course GENETICS 302 taught by Professor Hey during the Spring '11 term at Rutgers.

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feb_14_2011_lecture - Mapping Genes by Linkage &...

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