ANGENMAP Discussion Group

Sample Posts 2 

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

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