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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.

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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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Population-specific comparisons of map interval lengths. The - log10(p-values) measuring map interval differences are plotted in chromosomal order, with chromosomes shown in alternating colors for clarity. The green line indicates the p = 0.05 significance threshold while the red line indicates the Bonferroni-corrected significance threshold.
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Figure 2: Population-specific comparisons of map interval lengths. The - log10(p-values) measuring map interval differences are plotted in chromosomal order, with chromosomes shown in alternating colors for clarity. The green line indicates the p = 0.05 significance threshold while the red line indicates the Bonferroni-corrected significance threshold.

Mentions: We were able to perform eight population-specific comparisons, comparing map distance estimates in populations genotyped for the same screening sets (Table 4). The between-group comparisons are shown as Manhattan plots in Figure 2 and Q-Q plots in Additional File 6: Q-Q_plot.pdf. The chromosomal length comparisons are also illustrated in Figure 3. Since studies from the same screenset might have slight differences in the markers actually used, for each comparison, we compared maps constructed de novo using only the markers shared between the two groups. Therefore, since slightly different sets of markers are used, the resulting map lengths are specific to each analysis. For example, the Chinese map length when being compared to the European map is 4,036 cM, while it is 4,063 cM when compared to the Hispanic map. The Merlin program used for these analyses uses the Haldane map function, so our map lengths from these population comparisons are not directly comparable with Kosambi map lengths described elsewhere in this paper.


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)

Population-specific comparisons of map interval lengths. The - log10(p-values) measuring map interval differences are plotted in chromosomal order, with chromosomes shown in alternating colors for clarity. The green line indicates the p = 0.05 significance threshold while the red line indicates the Bonferroni-corrected significance threshold.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Population-specific comparisons of map interval lengths. The - log10(p-values) measuring map interval differences are plotted in chromosomal order, with chromosomes shown in alternating colors for clarity. The green line indicates the p = 0.05 significance threshold while the red line indicates the Bonferroni-corrected significance threshold.
Mentions: We were able to perform eight population-specific comparisons, comparing map distance estimates in populations genotyped for the same screening sets (Table 4). The between-group comparisons are shown as Manhattan plots in Figure 2 and Q-Q plots in Additional File 6: Q-Q_plot.pdf. The chromosomal length comparisons are also illustrated in Figure 3. Since studies from the same screenset might have slight differences in the markers actually used, for each comparison, we compared maps constructed de novo using only the markers shared between the two groups. Therefore, since slightly different sets of markers are used, the resulting map lengths are specific to each analysis. For example, the Chinese map length when being compared to the European map is 4,036 cM, while it is 4,063 cM when compared to the Hispanic map. The Merlin program used for these analyses uses the Haldane map function, so our map lengths from these population comparisons are not directly comparable with Kosambi map lengths described elsewhere in this paper.

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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