From kodouglas@tamu.edu Wed Jan 21 13:16:59 2009 From: "Kory Douglas" Date: Wed, 21 Jan 2009 13:07:37 -0600 Postmaster: submitted from web posting form To: Multiple Recipients of Subject: X-linked Linkage Mapping Anyone, I am working on a X-chromosome linkage map using STRs in Monodelphis domestica (opossum). I have ~30 markers with a 3 generation pedigree structure containing 571 individuals. I have genotype data and am using Crimap to construct the linkage map. We are familiar with Crimap using autosomal loci, but this is our first attempt at analyzing X-linked loci. All the significance values seem to be highly inflated. I do not know how to interpret the high LOD scores. It gives me LODs that are all over 100 in the two-point analysis and inflated scores in the flips analysis. Does anyone know how to interpret these scores so that I might get an idea of the strength of my order and/or does anyone have experience working with X-linked data and linkage mapping? Any help would be much appreciated. Cheers, Kory Douglas Texas A&M University

From yandell@stat.wisc.edu Wed Jan 21 13:35:32 2009 Date: Wed, 21 Jan 2009 13:35:32 -0600 From: Brian Yandell Reply-To: byandell@wisc.edu To: Multiple Recipients of Subject: Re: X-linked Linkage Mapping Kory, I recommend you read Broman KW, Sen S, Owens SE, Manichaikul A, Southard-Smith EM, Churchill GA (2006) The X chromosome in quantitative trait locus mapping. Genetics 174: 2151-2158. [doi:10.1534/genetics.106.061176] While this concerns inbreds, the issues remain. You will need to pay attention to the grandparents to sort out the X chr properly. Brian

From Paul.Fisher@agresearch.co.nz Fri Jan 23 03:04:39 2009 From: "Fisher, Paul" Date: Fri, 23 Jan 2009 22:04:38 +1300 To: Multiple Recipients of Subject: RE: X-linked Linkage Mapping Hi Kory I'm not sure off the top of my head what LOD scores you might expect from CRIMAP with your family design and no.s but you should get much higher levels of informative meioses for the X-chromosome than the autosomes e.g. I'm going to assume that you are tracing maternal grandsires' chromo somes through your pedigree(??) As no recombination happened (i.e. you have a known chromosome-long haplo type) when mat. grandsire passed his single X c/s to his daughter (the as sumed mother of your 3rd generation) you will end up with good knowledge of the phase of each of the mother's 2 X chromosomes. Higher inf. meioses should lead to higher LOD scores and if you add to the fact that you have multi-allelic (?) STRs this should hold up well for 2-point as well as multi-point analysis. FLIPS also should be sensitive to order as you've implied. In other words, you might yet be OK; feel free to email me if you wish to discuss this further cheers Paul Fisher AgResearch New Zealand

From ken.dodds@agresearch.co.nz Tue Jan 27 17:44:42 2009 From: "Dodds, Ken" Date: Wed, 28 Jan 2009 09:25:52 +1300 To: Multiple Recipients of Subject: RE: X-linked Linkage Mapping Hi Kroy, A couple of points that you may be aware of, but in case not ... You need to use sex-specific recombination rates. For the two point analysis, you will find that the male recombination rates are estimated as zero (assuming non-pseudoautosomal - I don't know if this is a factor for the opossum). (If they are not this might indicate genotyping errors). The lod score that is reported is for male and female rates being different from 0.5. A rough calculation says that the male component for 400-500 informative meioses would be 120-150. What you want is the lod for the female recombination (best estimate compared to 0.5). An example of how to do this follows (I've added *s around important parts of the output): LocA LocB rec. fracs.= 0.13 0.00, lods = *8.32* 6.63 7.60 8.18 8.31 8.31 8.26 8.16 8.03 7.87 7.68 7.47 *7.22* 8.31 8.19 7.66 6.97 6.25 5.50 4.73 3.93 3.13 2.36 1.66 1.10 Max lod(male & female) = 8.32 Max lod with female recombination set at 0.5 = 7.22 So lod for female component is 8.32-7.22=1.1 I don't think there are any special problems with flips for X-linked, as there is no information in the male meioses for ordering. Hope this helps, ________________________________________________________________ Ken Dodds AgResearch Email: ken.dodds@agresearch.co.nz Invermay Agricultural Centre Phone: (+64) 3 489-3809 Private Bag 50034 DDI: (+64) 3 489-9083 Mosgiel 9053, New Zealand FAX: (+64) 3 489-9037

Go back to the AnGenMap main page.