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Haplotype co‐segregation with attention deficit‐hyperactivity disorder in unrelated german multi‐generation families

Identifieur interne : 001767 ( Istex/Corpus ); précédent : 001766; suivant : 001768

Haplotype co‐segregation with attention deficit‐hyperactivity disorder in unrelated german multi‐generation families

Auteurs : Michelle K. Lin ; Christine M. Freitag ; Andrea B. Schote ; Haukur Pálmason ; Christiane Seitz ; Tobias J. Renner ; Marcel Romanos ; Susanne Walitza ; Christian P. Jacob ; Andreas Reif ; Andreas Warnke ; Rita M. Cantor ; Klaus-Peter Lesch ; Jobst Meyer

Source :

RBID : ISTEX:E19AEE13C27591E355457788DC299BAF62C10CE2

English descriptors

Abstract

Complex disorders have proved to be elusive in the search for underlying genetic causes. In the presence of large multi‐generation pedigrees with multiple affected individuals, heritable familial forms of the disorders can be postulated. Observations of particular chromosomal haplotypes shared among all affected individuals within pedigrees may reveal chromosomal regions, in which the disease‐related genes may be located. Hence, the biochemical pathways involved in pathogenesis can be exposed. We have recruited eight large Attention Deficit‐Hyperactivity Disorder (ADHD, OMIM: #143465) families of German descent. Densely spaced informative microsatellite markers with high heterozygosity rates were used to fine‐map and haplotype chromosomal regions of interest in these families. In three subsets and one full family of the eight ADHD families, haplotypes co‐segregating with ADHD‐affected individuals were identified at chromosomes 1q25, 5q11–5q13, 9q31–9q32, and 18q11–18q21. Positive LOD scores supported these co‐segregations. The existence of haplotypes co‐segregating among affected individuals in large ADHD pedigrees suggests the existence of Mendelian forms of the disorder and that ADHD‐related genes are located within these haplotypes. In depth sequencing of these haplotype regions can identify causative genetic mechanisms and will allow further insights into the clinico‐genetics of this complex disorder. © 2013 Wiley Periodicals, Inc.

Url:
DOI: 10.1002/ajmg.b.32192

Links to Exploration step

ISTEX:E19AEE13C27591E355457788DC299BAF62C10CE2

Le document en format XML

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<div type="abstract" xml:lang="en">Complex disorders have proved to be elusive in the search for underlying genetic causes. In the presence of large multi‐generation pedigrees with multiple affected individuals, heritable familial forms of the disorders can be postulated. Observations of particular chromosomal haplotypes shared among all affected individuals within pedigrees may reveal chromosomal regions, in which the disease‐related genes may be located. Hence, the biochemical pathways involved in pathogenesis can be exposed. We have recruited eight large Attention Deficit‐Hyperactivity Disorder (ADHD, OMIM: #143465) families of German descent. Densely spaced informative microsatellite markers with high heterozygosity rates were used to fine‐map and haplotype chromosomal regions of interest in these families. In three subsets and one full family of the eight ADHD families, haplotypes co‐segregating with ADHD‐affected individuals were identified at chromosomes 1q25, 5q11–5q13, 9q31–9q32, and 18q11–18q21. Positive LOD scores supported these co‐segregations. The existence of haplotypes co‐segregating among affected individuals in large ADHD pedigrees suggests the existence of Mendelian forms of the disorder and that ADHD‐related genes are located within these haplotypes. In depth sequencing of these haplotype regions can identify causative genetic mechanisms and will allow further insights into the clinico‐genetics of this complex disorder. © 2013 Wiley Periodicals, Inc.</div>
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<title level="a" type="main" xml:lang="en">Haplotype co‐segregation with attention deficit‐hyperactivity disorder in unrelated german multi‐generation families</title>
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<persName>
<forename type="first">Michelle K.</forename>
<surname>Lin</surname>
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<affiliation>Department of Neurobehavioral Genetics, University of Trier, Institute of Psychobiology, Trier, Germany</affiliation>
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<author xml:id="author-2">
<persName>
<forename type="first">Christine M.</forename>
<surname>Freitag</surname>
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<affiliation>Department of Child and Adolescent Psychiatry, Goethe University Frankfurt am Main, Frankfurt, Germany</affiliation>
</author>
<author xml:id="author-3">
<persName>
<forename type="first">Andrea B.</forename>
<surname>Schote</surname>
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<affiliation>Department of Neurobehavioral Genetics, University of Trier, Institute of Psychobiology, Trier, Germany</affiliation>
</author>
<author xml:id="author-4">
<persName>
<forename type="first">Haukur</forename>
<surname>Pálmason</surname>
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<affiliation>Department of Neurobehavioral Genetics, University of Trier, Institute of Psychobiology, Trier, Germany</affiliation>
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<persName>
<forename type="first">Christiane</forename>
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<affiliation>Department of Child and Adolescent Psychiatry, Saarland University Hospital, Homburg, Germany</affiliation>
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<persName>
<forename type="first">Tobias J.</forename>
<surname>Renner</surname>
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<affiliation>Department of Child and Adolescent Psychiatry and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany</affiliation>
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<persName>
<forename type="first">Marcel</forename>
<surname>Romanos</surname>
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<affiliation>Department of Child and Adolescent Psychiatry and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany</affiliation>
<affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Munich, Munich, Germany</affiliation>
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<persName>
<forename type="first">Susanne</forename>
<surname>Walitza</surname>
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<affiliation>Department of Child and Adolescent Psychiatry and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany</affiliation>
<affiliation>Department of Child and Adolescent Psychiatry and Psychotherapy, University of Zurich, Zurich, Switzerland</affiliation>
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<forename type="first">Christian P.</forename>
<surname>Jacob</surname>
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<affiliation>Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany</affiliation>
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<persName>
<forename type="first">Andreas</forename>
<surname>Reif</surname>
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<affiliation>Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany</affiliation>
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<author xml:id="author-11">
<persName>
<forename type="first">Andreas</forename>
<surname>Warnke</surname>
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<affiliation>Department of Child and Adolescent Psychiatry and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany</affiliation>
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<persName>
<forename type="first">Rita M.</forename>
<surname>Cantor</surname>
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<affiliation>Department of Human Genetics, University of California Los Angeles, School of Medicine, Los Angeles</affiliation>
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<persName>
<forename type="first">Klaus‐Peter</forename>
<surname>Lesch</surname>
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<affiliation>Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany</affiliation>
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<persName>
<forename type="first">Jobst</forename>
<surname>Meyer</surname>
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<email>meyerjo@uni-trier.de</email>
<affiliation>Department of Neurobehavioral Genetics, University of Trier, Institute of Psychobiology, Trier, Germany</affiliation>
<affiliation>Correspondence to:Prof. Jobst Meyer, University of Trier, Institute of Psychobiology, Department of Neurobehavioral Genetics, Johanniterufer 15, D54290 Trier, Germany.E‐mail:</affiliation>
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<title level="j">American Journal of Medical Genetics Part B: Neuropsychiatric Genetics</title>
<title level="j" type="abbrev">Am. J. Med. Genet.</title>
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<p>Complex disorders have proved to be elusive in the search for underlying genetic causes. In the presence of large multi‐generation pedigrees with multiple affected individuals, heritable familial forms of the disorders can be postulated. Observations of particular chromosomal haplotypes shared among all affected individuals within pedigrees may reveal chromosomal regions, in which the disease‐related genes may be located. Hence, the biochemical pathways involved in pathogenesis can be exposed. We have recruited eight large Attention Deficit‐Hyperactivity Disorder (ADHD, OMIM: #143465) families of German descent. Densely spaced informative microsatellite markers with high heterozygosity rates were used to fine‐map and haplotype chromosomal regions of interest in these families. In three subsets and one full family of the eight ADHD families, haplotypes co‐segregating with ADHD‐affected individuals were identified at chromosomes 1q25, 5q11–5q13, 9q31–9q32, and 18q11–18q21. Positive LOD scores supported these co‐segregations. The existence of haplotypes co‐segregating among affected individuals in large ADHD pedigrees suggests the existence of Mendelian forms of the disorder and that ADHD‐related genes are located within these haplotypes. In depth sequencing of these haplotype regions can identify causative genetic mechanisms and will allow further insights into the clinico‐genetics of this complex disorder. © 2013 Wiley Periodicals, Inc.</p>
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<term>ADHD</term>
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