An association analysis of candidate genes on chromosome 15 q11-13 and autism spectrum disorder.
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Autistic Disorder↗
Biomedical subjects
B M Neale
Publications and source records attributed to B M Neale.
Will haplotype maps be useful for finding genes?
From its introduction into the literature, the idea of haplotype map-based linkage disequilibrium (LD) studies has been the subject of disputes. These queries involve the extent to which the haplotype blocks exist, the validity of fundamental concepts such as the recombination hotspot, and the application of this idea in the form of the HapMap project. In this article, we review the relevant literature to evaluate the potential importance of haplotype maps for psychiatric genetics. We first take a closer look at the nature of haplotype blocks and then address the impact of block definitions and methodological factors, such as single-nucleotide polymorphism density and sample size, on findings from haplotype block studies. After distinguishing between two types of haplotype map-based LD studies, we discuss the importance of the recombination hotspot and the nature of the disease mutations affecting complex traits. In the final section, we summarize our main conclusions and comment on the usefulness of haplotype maps for finding genes.
Chromosome Mapping↗
No evidence for linkage or association of neuregulin-1 (NRG1) with disease in the Irish study of high-density schizophrenia families (ISHDSF).
The neuregulin-1 gene (NRG1) at chromosome 8p21-22 has been implicated as a schizophrenia susceptibility gene in Icelandic, Scottish, Irish and mixed UK populations. The shared ancestry between these populations led us to investigate the NRG1 polymorphisms and appropriate marker haplotypes for linkage and/or association to schizophrenia in the Irish study of high-density schizophrenia families (ISHDSF). Neither single-point nor multi-point linkage analysis of NRG1 markers gave evidence for linkage independent of our pre-existing findings telomeric on 8p. Analysis of linkage disequilibrium (LD) across the 252 kb interval encompassing the 7 marker core Icelandic/Scottish NRG1 haplotype revealed two separate regions of modest LD, comprising markers SNP8NRG255133, SNP8NRG249130 and SNP8NRG243177 (telomeric) and microsatellites 478B14-428, 420M9-1395, D8S1810 and 420M9-116I12 (centromeric). From single marker analysis by TRANSMIT and FBAT we found no evidence for association with schizophrenia for any marker. Haplotype analysis for the three SNPs in LD region 1 and, separately, the four microsatellites in LD region 2 (analyzed in overlapping 2-marker windows), showed no evidence for overtransmission of specific haplotypes to affected individuals. We therefore conclude that if NRG1 does contain susceptibility alleles for schizophrenia, they impact quite weakly on risk in the ISHDSF.
Chromosome Mapping↗