From mari0409_at_ufl.edu Wed Feb 15 13:42:08 2006 Subject: discrepancy between two-pt and multipoint analysis Date: Wed, 15 Feb 2006 13:49:16 -0500 From: "Mariasegaram,Maxy" <mari0409_at_ufl.edu> To: Multiple Recipients of <angenmap_at_animalgenome.org> Dear Colleagues, I am involved in mapping the gene responsible for the slick hair coat in Senepol derived cattle. The gene follows an autosomal dominant mode of inheritance, and the phenotype is being analysed as a binary trait in Superlink. My questions concerns the localisation of the gene using two- point and multi point linkage analyses. There appears to be a 5 cM discrepancy between the two methods in terms of the predicted location. I have checked my genotype data with Crimap's chrompic option to identify potential double recombinants and pedigree errors, but have found none. Has anyone else encountered similar problems and how do you resolve it? Thanks in advance for any suggestions. Cheers Max Maxy Mariasegaram USDA/ARS Subtropical Agricultural Research Station 22271 Chinsegut Hill Road Brooksville FL 34601 Tel: + 1 352-796-3385 x233 Fax: + 1 352-796-3520

From jheox_at_ntlworld.com Mon Feb 20 14:16:24 2006 From: jheox_at_ntlworld.com Subject: Re: discrepancy between two-pt and multipoint analysis Date: Mon, 20 Feb 2006 19:07:28 +0000 To: Multiple Recipients of <angenmap_at_animalgenome.org> Could I make some points that are not, I think, in doubt. 1. Two-point linkage analysis is based on well established assumptions and will only give problems if segregation is disturbed - most package programs assume Mendel's first law obeyed and proceed to estimate deviations from his second law. This is simple to check with dialelic loci. The statistical problem is similar to that presented by the human ABO blood-group locus. 2. Multi-locus analysis assumes the order known, as well as making assumptions on absence of sex difference in recombination and, in some programs, the 'backward look' of haplotyping parents from children. If it works then it should produce similar answers with less reliability on the mean but a lower variance, in which case it could have substantial advantages once checked against methods based on sounder assumptions and, unless marker order based on physical mapping, sounder data. Disturbed segregation can be due to various causes, of which the most obvious is the presence of recessive lethals from deficiencies. The established testing procedures do not distinguish homozygotes from hemizygotes. In some human disorders haplo-insufficiency can mimic dominant inheritance. As I am interested in mapping deficiencies in mammals I would welcome hearing more. John Edwards

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