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Closely linked cis-acting modifier of expansion of the CGG repeat in high risk FMR1 haplotypes.

Ennis S, Murray A, Brightwell G, Morton NE, Jacobs PA - Hum. Mutat. (2007)

Bottom Line: We found expansion status to be strongly associated with a approximately 50-kb region proximal to the fragile site.However, stratification of chromosomes by risk subgroups enabled us to identify a common SNP variant which cosegregates with the subset of D group haplotypes at highest risk of expansion (chi(1)(2)=17.84, p=0.00002).We have verified that this SNP acts as a marker of repeat expansion in three independent samples.

View Article: PubMed Central - PubMed

Affiliation: Genetic Epidemiology Group, Human Genetics (MP808), Southampton General Hospital, Southampton, United Kingdom. se@soton.ac.uk

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Related in: MedlinePlus

FIGURE 2. Unrooted phylogenetic tree representing the CCGA core haplogroup.The alleles for each of the four SNPs used to identify core groups are highlighted in blue (rs10521868, rs1805420, ATL1, FMRB).The six SNPs used in the subsequent stage of analysis are highlighted in red (rs17312728, rs1868140, and ss71651738 on the left–hand side; and rs6626286, rs12010481, and rs5904668 on the right–hand side).The black type that follows the SNP haplotype shows the DXS548–FRAXAC1–FRAXAC2 microsatellite haplotype followed by the corresponding microsatellite haplogroup and the number of observed instances of each haplotype (these data in black are for annotation purposes only and were not used in the phylogenetic analysis).The normal to expanded ratio of FRAXA chromosomes is shown for each branch.The branch onwhich the only observed primate haplotype co–occurs is identified by a green arrow. *Denotesmissing data.
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fig02: FIGURE 2. Unrooted phylogenetic tree representing the CCGA core haplogroup.The alleles for each of the four SNPs used to identify core groups are highlighted in blue (rs10521868, rs1805420, ATL1, FMRB).The six SNPs used in the subsequent stage of analysis are highlighted in red (rs17312728, rs1868140, and ss71651738 on the left–hand side; and rs6626286, rs12010481, and rs5904668 on the right–hand side).The black type that follows the SNP haplotype shows the DXS548–FRAXAC1–FRAXAC2 microsatellite haplotype followed by the corresponding microsatellite haplogroup and the number of observed instances of each haplotype (these data in black are for annotation purposes only and were not used in the phylogenetic analysis).The normal to expanded ratio of FRAXA chromosomes is shown for each branch.The branch onwhich the only observed primate haplotype co–occurs is identified by a green arrow. *Denotesmissing data.

Mentions: Results from a phylogenetic study conducted on a subset of the SNP data genotyped in our panel of 877 males, also distinguished ss71651738 as being of particular interest [Ennis, 2003]. In the first phase of the study, four SNPs located physically closest to FRAXA (rs10521868, rs1805420, ATL1, FMRB) were used to cluster chromosomes creating five “core haplogroups.” Microsatellite information was not used in the analysis. These SNP based haplogroups captured much of the group specific characteristics previously observed in the microsatellite based haplogroups. The “CCGA” core haplogroup was of particular interest. An unrooted phylogenetic tree of this group was created using the UPGMA option from the PHYLIP suite of software (Fig. 2) [Felsenstein, 1989]. The CCGA group contained 157 out of 159 of the D haplogroup chromosomes within our panel of 877 genotyped chromosomes. A solitary example from the C haplogroup was identified on the CCGA background and this particular chromosome was also unique in terms of its microsatellite composition. The addition of three SNPs proximal to the core SNPs (rs17312728, rs1868140, and ss71651738) and three SNPs distal (rs6626286, rs12010481, and rs5904668) generated an additional 14 subgroups.


Closely linked cis-acting modifier of expansion of the CGG repeat in high risk FMR1 haplotypes.

Ennis S, Murray A, Brightwell G, Morton NE, Jacobs PA - Hum. Mutat. (2007)

FIGURE 2. Unrooted phylogenetic tree representing the CCGA core haplogroup.The alleles for each of the four SNPs used to identify core groups are highlighted in blue (rs10521868, rs1805420, ATL1, FMRB).The six SNPs used in the subsequent stage of analysis are highlighted in red (rs17312728, rs1868140, and ss71651738 on the left–hand side; and rs6626286, rs12010481, and rs5904668 on the right–hand side).The black type that follows the SNP haplotype shows the DXS548–FRAXAC1–FRAXAC2 microsatellite haplotype followed by the corresponding microsatellite haplogroup and the number of observed instances of each haplotype (these data in black are for annotation purposes only and were not used in the phylogenetic analysis).The normal to expanded ratio of FRAXA chromosomes is shown for each branch.The branch onwhich the only observed primate haplotype co–occurs is identified by a green arrow. *Denotesmissing data.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2683060&req=5

fig02: FIGURE 2. Unrooted phylogenetic tree representing the CCGA core haplogroup.The alleles for each of the four SNPs used to identify core groups are highlighted in blue (rs10521868, rs1805420, ATL1, FMRB).The six SNPs used in the subsequent stage of analysis are highlighted in red (rs17312728, rs1868140, and ss71651738 on the left–hand side; and rs6626286, rs12010481, and rs5904668 on the right–hand side).The black type that follows the SNP haplotype shows the DXS548–FRAXAC1–FRAXAC2 microsatellite haplotype followed by the corresponding microsatellite haplogroup and the number of observed instances of each haplotype (these data in black are for annotation purposes only and were not used in the phylogenetic analysis).The normal to expanded ratio of FRAXA chromosomes is shown for each branch.The branch onwhich the only observed primate haplotype co–occurs is identified by a green arrow. *Denotesmissing data.
Mentions: Results from a phylogenetic study conducted on a subset of the SNP data genotyped in our panel of 877 males, also distinguished ss71651738 as being of particular interest [Ennis, 2003]. In the first phase of the study, four SNPs located physically closest to FRAXA (rs10521868, rs1805420, ATL1, FMRB) were used to cluster chromosomes creating five “core haplogroups.” Microsatellite information was not used in the analysis. These SNP based haplogroups captured much of the group specific characteristics previously observed in the microsatellite based haplogroups. The “CCGA” core haplogroup was of particular interest. An unrooted phylogenetic tree of this group was created using the UPGMA option from the PHYLIP suite of software (Fig. 2) [Felsenstein, 1989]. The CCGA group contained 157 out of 159 of the D haplogroup chromosomes within our panel of 877 genotyped chromosomes. A solitary example from the C haplogroup was identified on the CCGA background and this particular chromosome was also unique in terms of its microsatellite composition. The addition of three SNPs proximal to the core SNPs (rs17312728, rs1868140, and ss71651738) and three SNPs distal (rs6626286, rs12010481, and rs5904668) generated an additional 14 subgroups.

Bottom Line: We found expansion status to be strongly associated with a approximately 50-kb region proximal to the fragile site.However, stratification of chromosomes by risk subgroups enabled us to identify a common SNP variant which cosegregates with the subset of D group haplotypes at highest risk of expansion (chi(1)(2)=17.84, p=0.00002).We have verified that this SNP acts as a marker of repeat expansion in three independent samples.

View Article: PubMed Central - PubMed

Affiliation: Genetic Epidemiology Group, Human Genetics (MP808), Southampton General Hospital, Southampton, United Kingdom. se@soton.ac.uk

Show MeSH
Related in: MedlinePlus