| 1. |
- Kurbasic, Azra, et al.
(författare)
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Relative risks and effective number of meioses: A unified approach for general genetic models and phenotypes
- 2006
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Ingår i: Annals of Human Genetics. - : Wiley. - 1469-1809 .- 0003-4800. ; 70:6, s. 907-922
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Tidskriftsartikel (refereegranskat)abstract
- Many common diseases are known to have genetic components, but since they are non-Mendelian, i.e. a large number of genetic factors affect the phenotype, these components are difficult to localize. These traits are often called complex and analysis of siblings is a valuable tool for mapping them. It has been shown that the power of the affected relative pairs method to detect linkage of a disease susceptibility locus depends on the locus contribution to increased risk of relatives compared with population prevalence Risch, 1990a,b). In this paper we generalize calculation of relative risk to arbitrary phenotypes and genetic models, but also show that the relative risk can be split into the relative risk at the main locus and the relative risk due to interaction between the main locus and loci at other chromosomes. We demonstrate how the main locus contribution to the relative risk is related to probabilities of allele sharing identical by descent at the main locus, as well as power to detect linkage. To this end we use the effective number of meioses, introduced by Hossjer (2005a) as a convenient tool. Relative risks and effective number of meioses are computed for several genetic models with binary or quantitative phenotypes, with or without polygenic effects.
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| 2. |
- Lace, B., et al.
(författare)
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Age of SERPINA1 gene PI Z mutation: Swedish and Latvian population analysis
- 2008
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Ingår i: Annals of Human Genetics. - : Wiley. - 1469-1809 .- 0003-4800. ; 72:3, s. 300-304
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Tidskriftsartikel (refereegranskat)abstract
- Alpha 1-antitrypsin (A1AT) deficiency, one of the most common inborn errors of metabolism in Caucasians, is characterized by a low serum concentration of A1AT and a high risk of pulmonary emphysema and liver disease. The allelic frequency for the most common protease inhibitor (PI) Z mutation in the SERPINA1 gene is 2-5% in Caucasians of European descent. The objective of our study was to estimate the PI Z mutation age using molecular analysis in Latvian and Swedish populations, which have the highest frequency of PI Z mutation. DNA samples of heterozygous and homozygous PI Z allele carriers from Latvia (n = 21) and Sweden (n = 65) were analysed; 113 unrelated healthy donors from Latvia were used as a control group. MALDI-TOF analysis was performed on all samples. Pairwise Fst was computed to compare the PI Z mutation ages between the two populations and controls. A p value less than 0.05 was considered significant. Analysis of non-recombinant SNPs revealed that the PI Z mutation age was 2902 years in Latvia (SD 1983) and 2362 years in Sweden (SD 1614) which correlates with previous studies based on microsatellite analysis.
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| 3. |
- Sjakste, T., et al.
(författare)
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Association of microsatellite polymorphisms of the human 14q13.2 region with type 2 diabetes mellitus in latvian and finnish populations
- 2007
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Ingår i: Annals of Human Genetics. - : Wiley. - 1469-1809 .- 0003-4800. ; 71, s. 772-776
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Tidskriftsartikel (refereegranskat)abstract
- A polymorphic microsatellite in intron 6 of the human proteasome core particle PSMA6 gene (HSMS006), and four other microsatellites localized upstream on human chromosome 14q13.2 (HSMS801, HSMS702, HSMS701, HSMS602), were genotyped in 104 type 2 diabetic patients and 129 age-matched control subjects from Latvia and replicated in 91 type 2 diabetic patients and 88 age-matched healthy control subjects from the Botnia Study in Finland. In type 2 diabetic patients from both populations the HSMS006 (TG)22 allele was two times more frequent compared to the control group. In the Latvian population the (CAA)8 allele of the HSMS602 marker was less frequent in the diabetic group, as was the (AC)24 allele of microsatellite HSMS801. Allele frequencies of the HSMS701 and 702 repeats were similar in healthy controls and type 2 diabetic patients. In conclusion, our data suggest that variants in the PSMA6 gene on chromosome 14q13.2 are associated with type 2 diabetes.
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| 4. |
- Sjölander, Arvid, et al.
(författare)
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Fine Mapping of Disease Genes Using Tagging SNPs
- 2007
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Ingår i: Annals of Human Genetics. - : Wiley. - 1469-1809 .- 0003-4800. ; 71:6, s. 815-827
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Tidskriftsartikel (refereegranskat)abstract
- We describe a haplotype clustering approach for localising a disease mutation within a fixed genomic region, which supplements tagging SNP (tSNP) information with (external) information on linkage disequilibrium. By applying our method to simulated data based on the coalescent, and on real haplotype data, we demonstrate that there are situations where significant gains can be made by incorporating tagged SNPs into the analysis. The issues we explore are important not only to these types of studies, but also to studies that select tSNPs based on (external) HapMap phase II data, and those that use genome-wide markers.
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| 5. |
- Konings, A., et al.
(författare)
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Candidate gene association study for noise-induced hearing loss in two independent noise-exposed populations
- 2009
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Ingår i: Annals of Human Genetics. - : Wiley. - 0003-4800 .- 1469-1809. ; 73:2, s. 215-224
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Tidskriftsartikel (refereegranskat)abstract
- Millions of people are daily exposed to high levels of noise. Consequently, noise-induced hearing loss (NIHL) is one of the most important occupational health hazards worldwide. In this study, we performed an association study for NIHL based on a candidate gene approach. 644 Single Nucleotide Polymorphisms (SNPs) in 53 candidate genes were analyzed in two independent NIHL sample sets, a Swedish set and part of a Polish set. Eight SNPs with promising results were selected and analysed in the remaining part of the Polish samples. One SNP in PCDH15 (rs7095441), resulted in significant associations in both sample sets while two SNPs in MYH14 (rs667907 and rs588035), resulted in significant associations in the Polish sample set and significant interactions with noise exposure level in the Swedish sample set. Calculation of odds ratios revealed a significant association of rs588035 with NIHL in the Swedish high noise exposure level group. Our studies suggest that PCDH15 and MYH14 may be NIHL susceptibility genes, but further replication in independent sample sets is mandatory.
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| 6. |
- Lappalainen, T, et al.
(författare)
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Migration waves to the Baltic Sea region
- 2008
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Ingår i: Annals of Human Genetics. - Oxford : Blackwell Publishing. - 0003-4800 .- 1469-1809. ; 72, s. 337-348
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Tidskriftsartikel (refereegranskat)abstract
- In this study, the population history of the Baltic Sea region, known to be affected by a variety of migrations and genetic barriers, was analyzed using both mitochondrial DNA and Y-chromosomal data. Over 1200 samples from Finland, Sweden, Karelia, Estonia, Setoland, Latvia and Lithuania were genotyped for 18 Y-chromosomal biallelic polymorphisms and 9 STRs, in addition to analyzing 17 coding region polymorphisms and the HVS1 region from the mtDNA. It was shown that the populations surrounding the Baltic Sea are genetically similar, which suggests that it has been an important route not only for cultural transmission but also for population migration. However, many of the migrations affecting the area from Central Europe, the Volga-Ural region and from Slavic populations have had a quantitatively different impact on the populations, and, furthermore, the effects of genetic drift have increased the differences between populations especially in the north. The possible explanations for the high frequencies of several haplogroups with an origin in the Iberian refugia (H1, U5b, I1a) are also discussed.
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| 7. |
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| 8. |
- Pemberton, T.J., et al.
(författare)
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Using population mixture to optimize the utility of genomic databases: linkage disequilibrium and association study design in India
- 2008
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Ingår i: Annals of Human Genetics. - : Wiley. - 0003-4800 .- 1469-1809. ; 72:4, s. 535-546
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Tidskriftsartikel (refereegranskat)abstract
- When performing association studies in populations that have not been the focus of large-scale investigations of haplotype variation, it is often helpful to rely on genomic databases in other populations for study design and analysis – such as in the selection of tag SNPs and in the imputation of missing genotypes. One way of improving the use of these databases is to rely on a mixture of database samples that is similar to the population of interest, rather than using the single most similar database sample. We demonstrate the effectiveness of the mixture approach in the application of African, European, and East Asian HapMap samples for tag SNP selection in populations from India, a genetically intermediate region underrepresented in genomic studies of haplotype variation.
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| 9. |
- Zaros, C, et al.
(författare)
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On the origin of the transthyretin Val30Met familial amyloid polyneuropathy.
- 2008
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Ingår i: Annals of Human Genetics. - : Wiley. - 0003-4800 .- 1469-1809. ; 72:Pt 4, s. 478-84
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Tidskriftsartikel (refereegranskat)abstract
- Transthyretin (TTR) familial amyloid polyneuropathy is a severe autosomal dominant neuropathy of adulthood, frequently linked to the pathogenic Val30Met variant of the TTR gene. The condition was initially described in northern Portugal, which is the first focus of the disease. Other important clusters of families are found in Sweden, Japan and South America. The origin of the Val30Met mutation and its distribution through the populations remains unclear. In the present work, we aimed at refining the history of the Val30Met mutation in patients affected with TTR amyloid neuropathy from Portugal, Sweden and Brazil. The decay of haplotype sharing was studied in 60 patients to estimate the age of the Most Recent Common Ancestor (MRCA) of mutation carriers in these populations. Our results showed a common haplotype in Portuguese and Brazilian patients and an age estimate of the MRCA of 750 and 650 years, respectively. In contrast, a different haplotype was found in the Swedish Val30Met patients with a corresponding age estimate for the MRCA, of 375 years. This work strengthens the hypothesis of different founders in Portuguese and Swedish Val30Met carriers and suggested a Portuguese origin of the Brazilian mutation. The age estimates of the MRCA are in line with the current historical knowledge of these populations.
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