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Ancestry of the Timorese: age-related macular degeneration associated genotype and allele sharing among human populations from throughout the world.

Morrison MA, Magalhaes TR, Ramke J, Smith SE, Ennis S, Simpson CL, Portas L, Murgia F, Ahn J, Dardenne C, Mayne K, Robinson R, Morgan DJ, Brian G, Lee L, Woo SJ, Zacharaki F, Tsironi EE, Miller JW, Kim IK, Park KH, Bailey-Wilson JE, Farrer LA, Stambolian D, DeAngelis MM - Front Genet (2015)

Bottom Line: We genotyped 20 previously reported AMD-associated SNPs in the Timorese to examine their allele frequencies compared to and between previously documented AMD cohorts of varying ethnicities.The major risk allele of HTRA1 rs11200638 (10q26) was at a significantly higher frequency in the Timorese, as well as 3 of the 5 protective CFH (1q32) SNPs (rs800292, rs2284664, and rs12066959).Additionally, the most commonly associated AMD-risk SNP, CFH rs1061170 (Y402H), was also seen at a much lower frequency in the Korean and Timorese populations than in the assessed Caucasian populations (C ~7 vs. ~40%, respectively).

View Article: PubMed Central - PubMed

Affiliation: Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah Salt Lake City, UT, USA.

ABSTRACT
We observed that the third leading cause of blindness in the world, age-related macular degeneration (AMD), occurs at a very low documented frequency in a population-based cohort from Timor-Leste. Thus, we determined a complete catalog of the ancestry of the Timorese by analysis of whole exome chip data and haplogroup analysis of SNP genotypes determined by sequencing the Hypervariable I and II regions of the mitochondrial genome and 17 genotyped YSTR markers obtained from 535 individuals. We genotyped 20 previously reported AMD-associated SNPs in the Timorese to examine their allele frequencies compared to and between previously documented AMD cohorts of varying ethnicities. For those without AMD (average age > 55 years), genotype and allele frequencies were similar for most SNPs with a few exceptions. The major risk allele of HTRA1 rs11200638 (10q26) was at a significantly higher frequency in the Timorese, as well as 3 of the 5 protective CFH (1q32) SNPs (rs800292, rs2284664, and rs12066959). Additionally, the most commonly associated AMD-risk SNP, CFH rs1061170 (Y402H), was also seen at a much lower frequency in the Korean and Timorese populations than in the assessed Caucasian populations (C ~7 vs. ~40%, respectively). The difference in allele frequencies between the Timorese population and the other genotyped populations, along with the haplogroup analysis, also highlight the genetic diversity of the Timorese. Specifically, the most common ancestry groupings were Oceanic (Melanesian and Papuan) and Eastern Asian (specifically Han Chinese). The low prevalence of AMD in the Timorese population (2 of 535 randomly selected participants) may be due to the enrichment of protective alleles in this population at the 1q32 locus.

No MeSH data available.


Related in: MedlinePlus

Distribution of world haplogroups in the Timorese sample by continent. (A) Shows the distribution of the Y-STR haplogroups among the 248 Timorese males, grouped by the continent each haplogroup originated from. (B) Shows the distribution of the mtDNA haplogroups among the 535 Timorese subjects, grouped by the continent each haplogroup originated from.
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Figure 2: Distribution of world haplogroups in the Timorese sample by continent. (A) Shows the distribution of the Y-STR haplogroups among the 248 Timorese males, grouped by the continent each haplogroup originated from. (B) Shows the distribution of the mtDNA haplogroups among the 535 Timorese subjects, grouped by the continent each haplogroup originated from.

Mentions: The Y-STR analysis yielded genotypes for 265 of the 267 Timorese males. Using the publicly available databases World Haplogroup & Haplo-I Subclade Predictor (http://members.bex.net/jtcullen515/haplotest.htm) and Althey's Haplogroup Predictor (http://www.hprg.com/hapest5/), 11 haplogroups were assigned to 248 of these subjects (Figure 1A). The origin of the haplogroups is mostly Asia (73%), followed by Africa and Eurasia (13% each), and a small percent Oceana (1%) (Figure 2A).


Ancestry of the Timorese: age-related macular degeneration associated genotype and allele sharing among human populations from throughout the world.

Morrison MA, Magalhaes TR, Ramke J, Smith SE, Ennis S, Simpson CL, Portas L, Murgia F, Ahn J, Dardenne C, Mayne K, Robinson R, Morgan DJ, Brian G, Lee L, Woo SJ, Zacharaki F, Tsironi EE, Miller JW, Kim IK, Park KH, Bailey-Wilson JE, Farrer LA, Stambolian D, DeAngelis MM - Front Genet (2015)

Distribution of world haplogroups in the Timorese sample by continent. (A) Shows the distribution of the Y-STR haplogroups among the 248 Timorese males, grouped by the continent each haplogroup originated from. (B) Shows the distribution of the mtDNA haplogroups among the 535 Timorese subjects, grouped by the continent each haplogroup originated from.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496576&req=5

Figure 2: Distribution of world haplogroups in the Timorese sample by continent. (A) Shows the distribution of the Y-STR haplogroups among the 248 Timorese males, grouped by the continent each haplogroup originated from. (B) Shows the distribution of the mtDNA haplogroups among the 535 Timorese subjects, grouped by the continent each haplogroup originated from.
Mentions: The Y-STR analysis yielded genotypes for 265 of the 267 Timorese males. Using the publicly available databases World Haplogroup & Haplo-I Subclade Predictor (http://members.bex.net/jtcullen515/haplotest.htm) and Althey's Haplogroup Predictor (http://www.hprg.com/hapest5/), 11 haplogroups were assigned to 248 of these subjects (Figure 1A). The origin of the haplogroups is mostly Asia (73%), followed by Africa and Eurasia (13% each), and a small percent Oceana (1%) (Figure 2A).

Bottom Line: We genotyped 20 previously reported AMD-associated SNPs in the Timorese to examine their allele frequencies compared to and between previously documented AMD cohorts of varying ethnicities.The major risk allele of HTRA1 rs11200638 (10q26) was at a significantly higher frequency in the Timorese, as well as 3 of the 5 protective CFH (1q32) SNPs (rs800292, rs2284664, and rs12066959).Additionally, the most commonly associated AMD-risk SNP, CFH rs1061170 (Y402H), was also seen at a much lower frequency in the Korean and Timorese populations than in the assessed Caucasian populations (C ~7 vs. ~40%, respectively).

View Article: PubMed Central - PubMed

Affiliation: Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah Salt Lake City, UT, USA.

ABSTRACT
We observed that the third leading cause of blindness in the world, age-related macular degeneration (AMD), occurs at a very low documented frequency in a population-based cohort from Timor-Leste. Thus, we determined a complete catalog of the ancestry of the Timorese by analysis of whole exome chip data and haplogroup analysis of SNP genotypes determined by sequencing the Hypervariable I and II regions of the mitochondrial genome and 17 genotyped YSTR markers obtained from 535 individuals. We genotyped 20 previously reported AMD-associated SNPs in the Timorese to examine their allele frequencies compared to and between previously documented AMD cohorts of varying ethnicities. For those without AMD (average age > 55 years), genotype and allele frequencies were similar for most SNPs with a few exceptions. The major risk allele of HTRA1 rs11200638 (10q26) was at a significantly higher frequency in the Timorese, as well as 3 of the 5 protective CFH (1q32) SNPs (rs800292, rs2284664, and rs12066959). Additionally, the most commonly associated AMD-risk SNP, CFH rs1061170 (Y402H), was also seen at a much lower frequency in the Korean and Timorese populations than in the assessed Caucasian populations (C ~7 vs. ~40%, respectively). The difference in allele frequencies between the Timorese population and the other genotyped populations, along with the haplogroup analysis, also highlight the genetic diversity of the Timorese. Specifically, the most common ancestry groupings were Oceanic (Melanesian and Papuan) and Eastern Asian (specifically Han Chinese). The low prevalence of AMD in the Timorese population (2 of 535 randomly selected participants) may be due to the enrichment of protective alleles in this population at the 1q32 locus.

No MeSH data available.


Related in: MedlinePlus