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Enhanced genetic maps from family-based disease studies: population-specific comparisons.

He C, Weeks DE, Buyske S, Abecasis GR, Stewart WC, Matise TC, Enhanced Map Consorti - BMC Med. Genet. (2011)

Bottom Line: We found one map interval on chromosome 8p with a statistically significant size difference between the European and Chinese samples, and several map intervals with significant size differences between the African American and Chinese samples.When comparing Palauan with European samples, a statistically significant difference was detected at the telomeric region of chromosome 11p.Several significant differences were also identified between populations in chromosomal and genome lengths.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Genetics, Rutgers University, Piscataway, NJ, USA.

ABSTRACT

Background: Accurate genetic maps are required for successful and efficient linkage mapping of disease genes. However, most available genome-wide genetic maps were built using only small collections of pedigrees, and therefore have large sampling errors. A large set of genetic studies genotyped by the NHLBI Mammalian Genotyping Service (MGS) provide appropriate data for generating more accurate maps.

Results: We collected a large sample of uncleaned genotype data for 461 markers generated by the MGS using the Weber screening sets 9 and 10. This collection includes genotypes for over 4,400 pedigrees containing over 17,000 genotyped individuals from different populations. We identified and cleaned numerous relationship and genotyping errors, as well as verified the marker orders. We used this dataset to test for population-specific genetic maps, and to re-estimate the genetic map distances with greater precision; standard errors for all intervals are provided. The map-interval sizes from the European (or European descent), Chinese, and Hispanic samples are in quite good agreement with each other. We found one map interval on chromosome 8p with a statistically significant size difference between the European and Chinese samples, and several map intervals with significant size differences between the African American and Chinese samples. When comparing Palauan with European samples, a statistically significant difference was detected at the telomeric region of chromosome 11p. Several significant differences were also identified between populations in chromosomal and genome lengths.

Conclusions: Our new population-specific screening set maps can be used to improve the accuracy of disease-mapping studies. As a result of the large sample size, the average length of the 95% confidence interval (CI) for a 10 cM map interval is only 2.4 cM, which is considerably smaller than on previously published maps.

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Comparing map interval lengths between the Marshfield map and our enhanced map (Kosambi cM). The solid red triangle indicates a map interval on chromosome 20 with incorrect Marshfield map order (D20S451-D20S164: 11.16 cM in Marshfield map vs. 2.62 cM in our European map). The solid red square represents a map interval on chromosome 11 (D11S1999-D11S1981: 4.28 cM in Marshfield map vs. 11.31 cM in our map). Other map intervals exhibiting over two-fold difference in length are depicted with solid blue circles.
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Figure 1: Comparing map interval lengths between the Marshfield map and our enhanced map (Kosambi cM). The solid red triangle indicates a map interval on chromosome 20 with incorrect Marshfield map order (D20S451-D20S164: 11.16 cM in Marshfield map vs. 2.62 cM in our European map). The solid red square represents a map interval on chromosome 11 (D11S1999-D11S1981: 4.28 cM in Marshfield map vs. 11.31 cM in our map). Other map intervals exhibiting over two-fold difference in length are depicted with solid blue circles.

Mentions: The Weber screening sets were derived from the Marshfield map, and therefore we compared our map distance with the Marshfield map. Figure 1 shows many map intervals with large differences in map length. For example, at the map interval D20S451-D20S164 on chromosome 20 (depicted with a solid triangle), the Marshfield map has a map distance of 11.16 cM, while our map showed a map distance of 2.62 cM. This map interval has such a high length discrepancy because the order of these markers was different (incorrect) on the Marshfield map. Another map interval D11S1999-D11S1981 on chromosome 11 (depicted in a solid square) had a Marshfield map length of 4.28 cM, while our map showed a length of 11.31 cM. In this example the order of markers is consistent between our map and the Marshfield map. Use of imprecise map distances can impact the accuracy of multi-point linkage results. When different genetic map distances are used for the same linkage study, different conclusions could be reached. Since many map intervals differ greatly between the Marshfield map and our enhanced map, investigators who use Weber screensets should obtain more accurate linkage results by using our enhanced maps.


Enhanced genetic maps from family-based disease studies: population-specific comparisons.

He C, Weeks DE, Buyske S, Abecasis GR, Stewart WC, Matise TC, Enhanced Map Consorti - BMC Med. Genet. (2011)

Comparing map interval lengths between the Marshfield map and our enhanced map (Kosambi cM). The solid red triangle indicates a map interval on chromosome 20 with incorrect Marshfield map order (D20S451-D20S164: 11.16 cM in Marshfield map vs. 2.62 cM in our European map). The solid red square represents a map interval on chromosome 11 (D11S1999-D11S1981: 4.28 cM in Marshfield map vs. 11.31 cM in our map). Other map intervals exhibiting over two-fold difference in length are depicted with solid blue circles.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3037840&req=5

Figure 1: Comparing map interval lengths between the Marshfield map and our enhanced map (Kosambi cM). The solid red triangle indicates a map interval on chromosome 20 with incorrect Marshfield map order (D20S451-D20S164: 11.16 cM in Marshfield map vs. 2.62 cM in our European map). The solid red square represents a map interval on chromosome 11 (D11S1999-D11S1981: 4.28 cM in Marshfield map vs. 11.31 cM in our map). Other map intervals exhibiting over two-fold difference in length are depicted with solid blue circles.
Mentions: The Weber screening sets were derived from the Marshfield map, and therefore we compared our map distance with the Marshfield map. Figure 1 shows many map intervals with large differences in map length. For example, at the map interval D20S451-D20S164 on chromosome 20 (depicted with a solid triangle), the Marshfield map has a map distance of 11.16 cM, while our map showed a map distance of 2.62 cM. This map interval has such a high length discrepancy because the order of these markers was different (incorrect) on the Marshfield map. Another map interval D11S1999-D11S1981 on chromosome 11 (depicted in a solid square) had a Marshfield map length of 4.28 cM, while our map showed a length of 11.31 cM. In this example the order of markers is consistent between our map and the Marshfield map. Use of imprecise map distances can impact the accuracy of multi-point linkage results. When different genetic map distances are used for the same linkage study, different conclusions could be reached. Since many map intervals differ greatly between the Marshfield map and our enhanced map, investigators who use Weber screensets should obtain more accurate linkage results by using our enhanced maps.

Bottom Line: We found one map interval on chromosome 8p with a statistically significant size difference between the European and Chinese samples, and several map intervals with significant size differences between the African American and Chinese samples.When comparing Palauan with European samples, a statistically significant difference was detected at the telomeric region of chromosome 11p.Several significant differences were also identified between populations in chromosomal and genome lengths.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Genetics, Rutgers University, Piscataway, NJ, USA.

ABSTRACT

Background: Accurate genetic maps are required for successful and efficient linkage mapping of disease genes. However, most available genome-wide genetic maps were built using only small collections of pedigrees, and therefore have large sampling errors. A large set of genetic studies genotyped by the NHLBI Mammalian Genotyping Service (MGS) provide appropriate data for generating more accurate maps.

Results: We collected a large sample of uncleaned genotype data for 461 markers generated by the MGS using the Weber screening sets 9 and 10. This collection includes genotypes for over 4,400 pedigrees containing over 17,000 genotyped individuals from different populations. We identified and cleaned numerous relationship and genotyping errors, as well as verified the marker orders. We used this dataset to test for population-specific genetic maps, and to re-estimate the genetic map distances with greater precision; standard errors for all intervals are provided. The map-interval sizes from the European (or European descent), Chinese, and Hispanic samples are in quite good agreement with each other. We found one map interval on chromosome 8p with a statistically significant size difference between the European and Chinese samples, and several map intervals with significant size differences between the African American and Chinese samples. When comparing Palauan with European samples, a statistically significant difference was detected at the telomeric region of chromosome 11p. Several significant differences were also identified between populations in chromosomal and genome lengths.

Conclusions: Our new population-specific screening set maps can be used to improve the accuracy of disease-mapping studies. As a result of the large sample size, the average length of the 95% confidence interval (CI) for a 10 cM map interval is only 2.4 cM, which is considerably smaller than on previously published maps.

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