DNAprint Genomics (DNAG)

[mingwan0]

Here is another curious thing. At the Rowe Program in Human Genetics, University of California at Davis, they have also been looking at mapping by admixture linkage disequilibrium. Here are the abstracts of two papers.

Collins-Schramm HE, Phillips CM, Operario DJ, Lee JS, Weber JL, Hanson RL, Knowler WC, Cooper R, Li H, Seldin MF. Ethnic-difference markers for use in mapping by admixture linkage disequilibrium. Am J Hum Genet. 2002 Mar;70(3):737-50.

Mapping by admixture linkage disequilibrium (MALD) is a potentially powerful technique for the mapping of complex genetic diseases. The practical requirements of this method include (a) a set of markers spanning the genome that have large allele-frequency differences between the parental ethnicities contributing to the admixed population and (b) an understanding of the extent of admixture in the study population. To this end, a DNA-pooling technique was used to screen microsatellite and diallelic insertion/deletion markers for allele-frequency differences between putative representatives of the parental populations of the admixed Mexican American (MA) and African American (AA) populations. Markers with promising pooled differences were then confirmed by individual genotyping in both the parental and admixed populations. For the MA population, screening of >600 markers identified 151 ethnic-difference markers (EDMs) with delta>0.30 (where delta is the absolute value of each allele-frequency difference between two populations, summed over all marker alleles and divided by two) that are likely to be useful for MALD analysis. For the AA population, analysis of >400 markers identified 97 EDMs. In addition, individual genotyping of these markers in Pima Amerindians, Yavapai Amerindians, European American (EA) individuals, Africans from Zimbabwe, MA individuals, and AA individuals, as well as comparison to the CEPH genotyping set, suggests that the differences between subpopulations of an ethnicity are small for many markers with large interethnic differences. Estimates of admixture that are based on individual genotyping of these markers are consistent with a 60% EA:40% Amerindian contribution to MA populations and with a 20% EA:80% African contribution to AA populations. Taken together, these data suggest that EDMs with large interpopulation and small intrapopulation differences can be readily identified for MALD studies in both AA and MA populations.

Collins-Schramm HE, Chima B, Operario DJ, Criswell LA, Seldin MF. Markers informative for ancestry demonstrate consistent megabase-length linkage disequilibrium in the African American population. Hum Genet. 2003 Jun 3.

Admixture mapping is a potentially powerful tool for mapping complex genetic diseases. For application of this method, admixed individuals must have genomes composed of large segments derived intact from each founding population. Such segments are thought to be present in African Americans (AA) and should be demonstrable by examination of linkage disequilibrium (LD). Previous studies using a variety of polymorphic markers have variably reported long-range LD or rapid decay of LD. To further define the extent and characteristics of LD caused by admixture in the AA population, the current study utilized a set of 52 diallelic markers that were selected for large standard variances between putative representatives of the founder populations. LD was examined in over 250 marker-pairs, including linked markers from four different chromosomal regions and an equal number of matched unlinked comparisons. In the representative founder populations, strong LD was not observed for markers separated by more than 10 kb. In contrast, results indicated significant LD ( P<0.001, D'>0.3) in AA over large genomic segments exceeding 10 centiMorgans (cM) and 15 megabases (Mb). Only marginally significant LD was present between unlinked markers in this population, suggesting that choosing appropriate levels of significance for admixture mapping can minimize false positive results. The ability to detect LD for extended chromosomal segments in AA decayed not only as a function of the distance between markers, but also as a function of the standard variance of the markers. This examination of several genomic segments provides strong evidence that appropriate selection of informative markers is a crucial prerequisite for the application of admixture mapping to the AA population.

Now, they seem to have gone from "Ethnic Difference Markers" to "Markers informative for ancestry" (sounds suspiciously like Ancestry Informative Markers to me). So what happened between March 2002 and June 2003 that might have caused a change in "terminology", and is there a connection back to Shriver?

Collins-Schramm HE, Kittles RA, Operario DJ, Weber JL, Criswell LA, Cooper RS, Seldin MF. Markers that discriminate between European and African ancestry show limited variation within Africa. Hum Genet. 2002 Dec;111(6):566-9.

Markers informative for ancestry are necessary for admixture mapping and improving case-control association analyses. In particular, African Americans are an admixed population for which genetic studies require accurately evaluating admixture. This will require markers that can be used in African Americans to determine if a given genomic region is of European or African ancestry. This report shows that, despite studies indicating high intra-African sequence variation, markers with large inter-ethnic differences have only small variations in allele distribution among divergent African populations and should be valuable for evaluating admixture in complex disease genetic studies.

That name Collins-Schramm keeps appearing. She is one of Michael Seldin's graduate students.

http://mdphd.ucdavis.edu/students.htm

Heather Collins-Schramm - Genetics Graduate Group
I am currently beginning my fifth year of the M.D./Ph.D. program. I chose to integrate my medical and graduate studies, so I split the first two years of medical school (taking them over three years), and at the same time took all my graduate courses and began my Ph.D. research in Dr. Michael Seldin's laboratory. My Ph.D. will be in genetics, and I have a special interest in complex genetic diseases. During my first year I developed a rapid method for looking at microsatellite allele frequency differences between populations. I then used this method to identify markers with large differences between ethnicities that should be useful for a potentially powerful genome screening method known as Mapping by Admixture Linkage Disequilibrium (MALD). I have also examined characteristics of these markers such as allele frequency variations within populations and extent of linkage disequilibrium in various populations. Last I have been using markers to model disease status in analyses to better understand the power and limitations of the MALD method.