{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:54:13Z","timestamp":1791251653289,"version":"4.1.0"},"reference-count":36,"publisher":"BMJ","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2005,11]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    The haplotype H1 of the\n                    <jats:italic>tau<\/jats:italic>\n                    gene,\n                    <jats:italic>MAPT<\/jats:italic>\n                    , is highly associated with progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Objective:<\/jats:bold>\n                    To investigate the pathogenic basis of this association.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Detailed linkage disequilibrium and common haplotype structure of\n                    <jats:italic>MAPT<\/jats:italic>\n                    were examined in 27 CEPH trios using validated HapMap genotype data for 24 single nucleotide polymorphisms (SNPs) spanning\n                    <jats:italic>MAPT<\/jats:italic>\n                    .\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Multiple variants of the H1 haplotype were resolved, reflecting a far greater diversity of\n                    <jats:italic>MAPT<\/jats:italic>\n                    than can be explained by the H1 and H2 clades alone. Based on this, six haplotype tagging SNPs (htSNPs) that capture 95% of the common haplotype diversity were used to genotype well characterised PSP and CBD case\u2013control cohorts. In addition to strong association with PSP and CBD of individual SNPs, two common haplotypes derived from these htSNPs were identified that are highly associated with PSP: the sole H2 derived haplotype was underrepresented and one of the common H1 derived haplotypes was highly associated, with a similar trend observed in CBD. There were powerful and highly significant associations with PSP and CBD of haplotypes formed by three H1 specific SNPs. This made it possible to define a candidate region of at least \u223c56 kb, spanning sequences from upstream of\n                    <jats:italic>MAPT<\/jats:italic>\n                    exon 1 to intron 9. On the H1 haplotype background, these could harbour the pathogenic variants.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    The findings support the pathological evidence that underlying variations in\n                    <jats:italic>MAPT<\/jats:italic>\n                    could contribute to disease pathogenesis by subtle effects on gene expression and\/or splicing. They also form the basis for the investigation of the possible genetic role of\n                    <jats:italic>MAPT<\/jats:italic>\n                    in Parkinson\u2019s disease and other tauopathies, including Alzheimer\u2019s disease.\n                  <\/jats:p>","DOI":"10.1136\/jmg.2005.031377","type":"journal-article","created":{"date-parts":[[2005,3,25]],"date-time":"2005-03-25T20:13:07Z","timestamp":1111781587000},"page":"837-846","source":"Crossref","is-referenced-by-count":231,"title":["Linkage disequilibrium fine mapping and haplotype association analysis of the\n                    <i>tau<\/i>\n                    gene in progressive supranuclear palsy and corticobasal degeneration"],"prefix":"10.1136","volume":"42","author":[{"given":"A M","family":"Pittman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A 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