Genomic Screening for Genes Predisposing to Bipolar Disease

Berrettini, Wade H.; Detera‐Wadleigh, Sevilla D.; Goldin, Lynn R.; Martínez, María del Carmen Jiménez; Hsieh, Wang-Ting; Hoehe, Margaret R.; Choi, Henry; Muniec, David; Ferraro, Thomas N.; Guroff, Juliet G.; Kazuba, Diane; Harris, Nina; Kron, Eric; Nürnberger, John I.; Alexander, Robert; Gershon, Elliot S.

doi:10.1097/00041444-199203000-00004

Cited by 19 publications

(15 citation statements)

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“…ration) have identified a clone on 18p that shows association with BP illness in this sample, as well as in the sample described in Berrettini et al [1991]. The evidence for a locus on 18q continues to be substantial (McMahon et al, in preparation), and the modest allele sharing seen here on D18S70 tends to support that.…”

Section: Discussionsupporting

confidence: 62%

Genomic survey of bipolar illness in the NIMH genetics initiative pedigrees: A preliminary report

Nürnberger

DePaulo²,

Gershon³

et al. 1997

Am. J. Med. Genet.

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119

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Four sites collaborated with the NIMH to develop a resource for the genetic study of bipolar (BP) illness. Common methods of ascertainment and assessment were developed in 1989. A series of families with a bipolar I (BPI) proband and at least one BPI or schizoaffective, bipolar type (SA/BP) first-degree relative has been studied. We now report initial data from a genomic survey with an average intermarker interval of 10 cM on 540 subjects from 97 families. This is the largest commonly ascertained and assessed linkage sample for bipolar illness reported to date; it includes 232 subjects with BPI, 32 SA/BP, 72 bipolar II (BPII), and 88 unipolar, recurrent (UPR). Nonparametric methods of analysis were employed, with all sites using affected sib pair analysis. The strongest findings thus far appear to be on chromosomes 1, 6, 7, 10, 16, and 22. Support has also been found for some previously reported linkages, including 21q and possibly Xq26. All these areas (as well as others) will be followed up with additional markers and further analyses. No locus tested thus far meets stringent criteria for an initial finding of significant linkage. Am. J. Med. Genet. 74:227-237, 1997. © 1997 Wiley-Liss, Inc.KEY WORDS: bipolar affective disorder; genetics; linkage; genomic survey; nonparametric analysis INTRODUCTIONBipolar affective disorder (BP) is a disabling condition involving dysregulation of multiple physiologic functions, including mood, appetite, sleep, and activity [Goodwin and Jamison, 1990]. It occurs in about 1% of the population, with usual onset in young adulthood. With appropriate management the condition is substantially treatment-responsive, but episodes tend to recur throughout life. This condition has long been observed to aggregate within families [Nurnberger et al., 1994b]. Twin and adoption studies suggest significant heritable risk factors [Bertelsen et al., 1977;Mendlewicz and Rainer, 1977]. The genetics of BP illness is complex, with segregation analyses generally not consistent with single major locus inheritance [Nurnberger et al., 1994b]. No pathognomonic biochemical abnormality is currently known to be present, and diagnosis is based on clinical history and presentation.Following the successful identification of linkage of Huntington disease to markers on chromosome 4 [Gusella et al., 1983], the interest of investigators in psychiatric genetics moved toward the application of molecular methods to the major psychiatric disorders. The paradigm for Mendelian disorders at that time was the identification of single large pedigrees with multiple cases of illness over several generations, and analysis of restriction fragment length polymorphism (RFLP) variation within the pedigree using the LOD score method. Egeland et al. [1987] reported linkage between BP and markers on chromosome 11p15 in a large Amish family. Subsequent studies in other samples, however, did not confirm this finding [DeteraWadleigh et al., 1987;Hodgkinson et al., 1987], and a later analysis in the same family, with additional clinical i...

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Section: Discussionsupporting

confidence: 62%

Genomic survey of bipolar illness in the NIMH genetics initiative pedigrees: A preliminary report

Nürnberger

DePaulo²,

Gershon³

et al. 1997

Am. J. Med. Genet.

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119

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“…Although LOD scores obtained at locus D1S103 seemed encouraging at fIrst, they could have arisen by chance, given the number of linkage tests per formed. Furthermore, in the previous published anal ysis of this region in these pedigrees (Berrettini et al 1991b), the nearby markers did not suggest linkage. However, it is worth mentioning that positive LOD scores on chromosome 1q had been previously reported in the Old Order Amish pedigree 110 at loci in the same area (Pakstis et a1.…”

Section: Discussionmentioning

confidence: 59%

“…At young ages, the rate of pheno copies is 22%, but at older ages the rate of phenocopies increases up to 37%. Our model, with some particular family structures that include affected individuals lo cated in the higher phenocopy penetrances class, would lead to less extreme LaD scores than previously calcu lated (Berrettini et al 1991b). We assumed equal recom bination in males and females for the initial analysis.…”

Section: Ceaotyping and Linkage Analysismentioning

confidence: 91%

“…Berrettini et al (1991a) described a series of 21 pedigrees with BP. Genetic linkage of illness in this ped igree series has been examined in previously published papers for 107 markers on chromosomes 1, 10q, llq, 13, 15, and 17 (Berrettini et al 1991b), for 24 markers on chromosome 5 in 14 of these pedigrees (Detera Wadleigh et al 1992), and for fI.ve markers on Xq27-28 in a subset of families in which segregation of BP is con sistent with X-chromosome transmission Gejman et al 1990), with classic restriction frag ment length polymorphism (RFLP) markers used for 0893-133X/93/$O.OO nearly all loci. Here we report linkage analyses of 57 additional markers, all micro satellites, to BP.…”

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confidence: 99%

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Linkage Analysis of Fifty-Seven Microsatellite Loci to Bipolar Disorder

Gejman¹,

Martínez

Cao³

et al. 1993

Neuropsychopharmacol

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authors' goal was to screen for genetic linkage with mghly infonnative deoxyribonucleic acid (DNA)Urosatellite markers on a series of moderately sized HDrth American bipolar disorder (BP) pedigrees. These IP pedigrees were genotyped with 57 short tandem rrptIlt polymorphic systems (microsatellites) that were tcymIltiCll lly amplified from genomic DNA. We did not ,., significant evidence for genetic linkage. We found II\' WORDS: Mapping; Bipolar illness; Microsatellites; Gmtti c linkage simulations; GNASl; Human X-linked GABA-A receptor a3-subunit gene A body of epidemiologic studies implies that there is l&metic component that confers susceptibility to bipo

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“…We have been conducting a genomic search for BP vulnerability genes, using a series of multiplex BP families (20)(21)(22). We report here results for analysis of several pericentromeric chromosome 18 DNA markers (23) A minisatellite probe (cMS615) for locus D18S32 was a gift from John Armour (University of Leiceister, U.K.).…”

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confidence: 99%

Chromosome 18 DNA markers and manic-depressive illness: evidence for a susceptibility gene.

Berrettini

Ferraro

Goldin

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

328

236

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In the course of a systematic genomic survey, 22 mani-depressive (bipolar) families were ea for linkage to 11 chromosome 18 pericentromeric marker loci, under dominant and recessive models. Overall logarithm of odds score analysis for the pedigree series was not s cant under either model, but several families yielded logarithm of odds scores consistent with linkage under dominant or recessive models.Affected sibling pair analysis of these data yielded evidence for linkage (P < 0.001) at D18S21. Affected pedigree member analysis also suggests linkage, with multilocus results for five loci giving P < 0.0001 and P = 0.0007 for weighting functions Ap) = 1 and l/V-A, respectively, where p is the allele frequency. These results imply a susceptibility gene in the pericentromeric region of chromosome 18, with a complex mode of inheritance.TWo plausible a te genes, a corticotropin receptor and the a subunit of a GTP bind protein, have been localized to this region.Evidence from twin, family, and adoption studies suggests that bipolar (BP) illness is, in part, a heritable disease (1). Linkage studies of BP disorder have been conducted to localize causative genes; however, no confirmed linkages have been established. Evidence for a BP gene on llplS (2) has been discounted by failure to replicate the finding in numerous other pedigrees (3-6) and by evaluation of newly ascertained individuals in the original pedigree (7). The color-vision region of Xq28 also has been reported linked to BP illness (8)(9)(10)(11)

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Genomic Screening for Genes Predisposing to Bipolar Disease

Cited by 19 publications

References 0 publications

Genomic survey of bipolar illness in the NIMH genetics initiative pedigrees: A preliminary report

Genomic survey of bipolar illness in the NIMH genetics initiative pedigrees: A preliminary report

Linkage Analysis of Fifty-Seven Microsatellite Loci to Bipolar Disorder

Chromosome 18 DNA markers and manic-depressive illness: evidence for a susceptibility gene.

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