Topic: Information provided by linkage or identity by descent in sequencing studies of highly heritable diseases
Faculty contact: Sharon Browning. sguy@uw.edu
October 13: Those who attended the American Society of Human Genetics meeting will report to the rest of us.
October 20: Tracy, Jean (Bruce)
M. Boehnke 1994 Limits of resolution of genetic linkage studies: implications for the positional cloning of human disease genes. Am J Hum Genet 55:379-390.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1918352/pdf/ajhg00041-0166.pdf
This paper points out that although linkage information can yield a region harboring the disease-causing mutation, the region is typically quite wide.
October 27: Yatong, Xiaowen (Ellen)
Sobreira et al. 2010 Whole-genome sequencing of a single proband together with linkage analysis identifies a Mendelian disease gene. Plos Genetics 6:e1000991.
http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1000991
This study used whole genome sequence on just one case, in concert with linkage peak information to find the causal variant.
November 3: Bowen, Jenn (Tim)
Bowden et al. 2010 Molecular basis of a linkage peak: exome sequencing and family-based analysis identify a rare genetic variant in the ADIPOQ gene in the IRAS family study. Hum. Mol. Genet. 19: 4112-4120.
http://hmg.oxfordjournals.org/content/19/20/4112.full
This study used family-specific linkage analysis to choose which families to pursue for whole exome sequencing.
November 10: Eric, Aaron (Liz)
Rodelsperger et al. 2011 Identity-by-descent filtering of exome sequence data for disease-gene identification in autosomal recessive disorders. Bioinformatics 27:829-836
http://bioinformatics.oxfordjournals.org/content/27/6/829
This paper develops a method for finding positions at which all affected siblings with a recessive disease share both haplotypes IBD, as a means of filtering the genome.
November 17: Fiona, Anya (Ellen)
Louis-Dit-Picard et al. 2012 KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron. Nature Genetics 44, 456-460
http://www.nature.com/ng/journal/v44/n4/full/ng.2218.html
This paper used weak linkage signals in family data to prioritize regions in which to look for candidate missense variants.
November 24: Caitlin, Taryn (Sharon)
Bull et al. 2013 Unlocking the bottleneck in forward genetics using whole-genome sequencing and identity by descent to isolate causative mutations. PLoS Genet 9(1): e1003219
http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1003219
This paper uses IBD mapping and sequencing in mice from a forward genetic experiment to identify the mutations responsible for changes in phenotype.
December 1: Alice, Serge (Liz)
Koboldt et al. 2014 Exome-based mapping and variant prioritization for inherited Mendelian disorders. Am J Hum Genet 94:373-384
http://www.sciencedirect.com/science/article/pii/S0002929714000548
This paper presents a system for scoring candidate variants that includes identity by descent sharing between affected family members.
Also see the author summary at:
http://massgenomics.org/2014/03/variant-prioritization-in-rare-disorders.html
December 8: Brayan, Kelsey (Sharon)
N. H. Chapman et al. 2015 Whole exome sequencing in extended families with autism spectrum disorder implicates four candidate genes. Human Genetics 134:1055-1068
http://link.springer.com/article/10.1007/s00439-015-1585-y/fulltext.html
This paper from Ellen Wijsman's group considers several strategies for analysis of sequence data from families for a complex disease.
Additional reading:
J. E. Bailey-Wilson and A. F. Wilson 2011 Linkage analysis in the next-generation sequencing era. Human Heredity 72:228-236.
http://www.karger.com/Article/Pdf/334381
This paper reviews linkage analysis in the context of sequencing studies.