No evidence for linkage of chromosome 6p markers to schizophrenia in Southern African Bantu-speaking families

Bp, Riley; Rajagopalan, S; Mogudi-Carter, M.; Jenkins, Trefor; Williamson, Robert

doi:10.1097/00041444-199622000-00003

Cited by 27 publications

(13 citation statements)

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“…These families have been described in detail elsewhere (Riley et al, 1996a;Riley et al, 1996b;Riley et al, 1997;Riley et al, 1998). Microsatellite markers were amplified using standard PCR conditions and publicly available primer sequences.…”

Section: Methodsmentioning

confidence: 99%

Haplotype transmission disequilibrium and evidence for linkage of the CHRNA7 gene region to schizophrenia in Southern African Bantu families

Riley¹,

Makoff²,

Mogudi-Carter

et al. 2000

Am. J. Med. Genet.

114

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Recent reports have strongly linked markers near the alpha-7 nicotinic cholinergic receptor subunit gene on human chromosome 15q13-q14 to a sensory gating deficit common in schizophrenics, and have shown positive though non-significant results linking this region to the primary phenotype of schizophrenia in a sample of North American families. We therefore tested for linkage between markers in this region of chromosome 15q and schizophrenia in a sample of 15 multiply affected and 5 single case families with schizophrenia drawn from the Bantu-speaking black population of South Africa. An initial replication using markers from the original study gave an affected-only LOD score maximum of 1.08 under a recessive model at Theta=0.00 for D15S1360, a dinucleotide polymorphism found on the same YAC as the alpha-7 receptor gene. Nonparametric affected-only multipoint analysis gave a Z-score of 1. 29, P=0.098, for D15S1360, and Z=1.45, p=0.075 for D15S118. We then increased the resolution of the map with an extended set of 20 markers. Again, two peaks were observed, with NPL scores of 1.81, p=0.037, at D15S1043 and 1.79 at D15S1360 and 1.80 at D15S1010, both p=0.037. Transmission disequilibrium testing of data from D15S1360 gave an allele-wise and genotype-wise chi(2) of 6.59, 2 df, p=0.037. Haplotype transmission disequilibrium testing using a restricted allele and haplotype set from D15S1043 and D15S1360 gave a global chi(2) of 10.647, 4 df, P=0.007, and a maximum chi(2) of 6.567, 1 df, P=0.004 for excess transmission of the 1.2 haplotype into affected offspring. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:196-201, 2000.

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Section: Methodsmentioning

confidence: 99%

Haplotype transmission disequilibrium and evidence for linkage of the CHRNA7 gene region to schizophrenia in Southern African Bantu families

Riley¹,

Makoff²,

Mogudi-Carter

et al. 2000

Am. J. Med. Genet.

114

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“…Other replication attempts failed. [35][36][37][38][39] A collaborative multicenter study, which included most of the samples of schizophrenia families held around the world, found increased allele sharing of 55.9% and a multipoint maximum likelihood score (MLS) of 2.19 (P ¼ 0.001) excluding the ISHDSF and 2.68 (P ¼ 0.0004) including the ISHDSF families. 40 Two meta-analyses provided strong support for linkage to several markers in the 6p region, 41,42 one did not.…”

Section: Introductionmentioning

confidence: 99%

Identification of a high-risk haplotype for the dystrobrevin binding protein 1 (DTNBP1) gene in the Irish study of high-density schizophrenia families.

et al. 2003

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A recent report showed significant associations between several SNPs in a previously unknown EST cluster with schizophrenia. 1 The cluster was identified as the human dystrobrevin binding protein 1 gene (DTNBP1) by sequence database comparisons and homology with mouse DTNBP1. 2 However, the linkage disequilibrium (LD) among the SNPs in DTNBP1 as well as the pattern of significant SNP-schizophrenia association was complex. This raised several questions such as the number of susceptibility alleles that may be involved and the size of the region where the actual disease mutation(s) could be located. To address these questions, we performed different single-marker tests on the 12 previously studied and 2 new SNPs in DTNBP1 that were re-scored using an improved procedure, and performed a variety of haplotype analyses. The sample consisted of 268 Irish multiplex families selected for high density of schizophrenia. Results suggested a simple structure where the LD in the target region could be explained by 6 haplotypes that together accounted for 96% of haplotype diversity in the whole sample. From these six, a single high-risk haplotype was identified that showed a significant association with schizophrenia and explained the pattern of significant findings in the analyses with individual markers. This haplotype was 30 kb long, had a large effect, could be measured with two tag SNPs only, had a frequency of 6% in our sample, seemed to be of relatively recent origin in evolutionary terms, and was equally distributed over Ireland. Implications of these findings for follow-up and replication studies are discussed.

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“…Riley and collaborators were the first to investigate schizophrenia in a South African population and published a series of manuscripts on linkage analyses in a cohort of Bantu-speaking black South Africans. [17][18][19][20][21][22] Areas of implied linkage to schizophrenia identified by these studies are displayed in Table II and include genomic regions surrounding the coding regions for subunits of N-methyl-D-aspartate (NMDA) receptors 19 and the alpha7 acetylcholine receptor gene (CHRNA7). 22 NMDA receptors form part of the glutamate system, which is believed to be of relevance as NMDA antagonists (i.e.…”

Section: Schizophreniamentioning

confidence: 99%

Psychiatric genetics in South Africa: cutting a rough diamond

Wright¹,

Niehaus²,

Koen³

et al. 2011

Afr. J. Psych

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Psychiatric disorders place a considerable healthcare burden on South African society. Incorporating genetic technologies into future treatment plans offers a potential mechanism to reduce this burden. This review focuses on psychiatric genetic research that has been performed in South African populations with regards to obsessive-compulsive disorder, schizophrenia and bipolar disorder. Preliminary findings from these studies suggest that data obtained in developed countries cannot necessarily be extrapolated to South African population groups. Psychiatric genetic studies in South Africa seem to involve relatively low-cost methodologies and only a limited number of large national collaborative studies. Future research in South Africa should therefore aim to incorporate highthroughput technologies into large scale psychiatric studies through the development of collaborations. On a global level, the vast majority of psychiatric genetic studies have been performed in non-African populations. South Africa, as the leading contributor to scientific research in Africa, may provide a foundation for addressing this disparity and strengthening psychiatric genetic research on the continent. Although the elucidation of the genetic architecture of psychiatric disorders has proved challenging, examining the unique genetic profiles found in South African populations could provide valuable insight into the genetics of psychiatric disorders. 356 pharmacogenetic studies). The Afrikaners are an example of a homogenous population as they arose from a small founder population of 1000-2000 Dutch immigrants that arrived in South Africa in the 17th century. 6,7 The ancient southern African Khoisan population possesses the highest level of genetic diversity reported to date, while the Mixed Ancestry population shows the greatest global admixture of any of the world's populations analysed thus far. 8 Additionally, the Nguni-speaking Xhosa population shows a significant genetic contribution from the Khoisan in their genomes, reflecting admixture between these ancient individuals and ancestral Bantu populations; artefacts of this exchange are also linguistically evident through the click consonants present in the isiXhosa language. 8,9 The prevalence of psychiatric disorders in the different ethnic groups of South Africa is not known, although evidence from the South African Stress and Health Study 10 suggests very little difference from non-African populations. However, alarmingly, it appears that the majority of individuals suffering from psychiatric disorders in South Africa do not receive treatment. 11 Revised burden of disease estimates place neuropsychiatric disorders as the third highest cause of disability-adjusted life years in the country, mainly due to the extended morbidity of such conditions. 12 Unipolar depression, alcohol use, bipolar affective disorder, schizophrenia, drug use, obsessive-compulsive disorder (OCD) and panic disorder are neuropsychiatric disorders that fall into the top 20 causes of years lived with ...

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No evidence for linkage of chromosome 6p markers to schizophrenia in Southern African Bantu-speaking families

Cited by 27 publications

References 0 publications

Haplotype transmission disequilibrium and evidence for linkage of the CHRNA7 gene region to schizophrenia in Southern African Bantu families

Haplotype transmission disequilibrium and evidence for linkage of the CHRNA7 gene region to schizophrenia in Southern African Bantu families

Identification of a high-risk haplotype for the dystrobrevin binding protein 1 (DTNBP1) gene in the Irish study of high-density schizophrenia families.

Psychiatric genetics in South Africa: cutting a rough diamond

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