Analysis of a t(18;21)(p11.1;p11.1) translocation in a family with schizophrenia

Meerabux, Joanne; Ohba, Hideki; Iwayama, Yoshimi; Maekawa, Motoko; Detera‐Wadleigh, Sevilla D.; DeLisi, Lynn E.; Yoshikawa, Takeo

doi:10.1038/jhg.2009.47

Cited by 8 publications

(4 citation statements)

References 23 publications

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“…In addition to these findings, suggestive linkage was reported in a non-parametric linkage analysis of a data set of 22 Caucasian families [47] and in an association study of 363 parent-child trios of Caucasian descent [48]. Finally, the microsatellite marker with the highest linkage signal on chromosome 18 detected in our study ( D18S453 ) maps less than 1 Mb distal to the translocation breakpoint [t(18;21)(p11.1;p11.1)] segregating with schizophrenia in a seven member family [49]. A number of groups reported evidence for linkage for bipolar and other psychiatric disorders in the 4p15.2–4p16.3 region (see references in [47], [50]–[53]), including a genome-wide linkage study of mental health wellness in the Old Order Amish which found significant evidence for linkage on chromosome 4p, about 5 Mb distal of the peak we detected [53].…”

Section: Resultssupporting

confidence: 51%

Genomic View of Bipolar Disorder Revealed by Whole Genome Sequencing in a Genetic Isolate

et al. 2014

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Bipolar disorder is a common, heritable mental illness characterized by recurrent episodes of mania and depression. Despite considerable effort to elucidate the genetic underpinnings of bipolar disorder, causative genetic risk factors remain elusive. We conducted a comprehensive genomic analysis of bipolar disorder in a large Old Order Amish pedigree. Microsatellite genotypes and high-density SNP-array genotypes of 388 family members were combined with whole genome sequence data for 50 of these subjects, comprising 18 parent-child trios. This study design permitted evaluation of candidate variants within the context of haplotype structure by resolving the phase in sequenced parent-child trios and by imputation of variants into multiple unsequenced siblings. Non-parametric and parametric linkage analysis of the entire pedigree as well as on smaller clusters of families identified several nominally significant linkage peaks, each of which included dozens of predicted deleterious variants. Close inspection of exonic and regulatory variants in genes under the linkage peaks using family-based association tests revealed additional credible candidate genes for functional studies and further replication in population-based cohorts. However, despite the in-depth genomic characterization of this unique, large and multigenerational pedigree from a genetic isolate, there was no convergence of evidence implicating a particular set of risk loci or common pathways. The striking haplotype and locus heterogeneity we observed has profound implications for the design of studies of bipolar and other related disorders.

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Section: Resultssupporting

confidence: 51%

Genomic View of Bipolar Disorder Revealed by Whole Genome Sequencing in a Genetic Isolate

et al. 2014

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“…A remarkable number of genes implicated in ASD or NDD by single gene disruption from BCAs in our study have also been recently associated with a spectrum of developmental, psychiatric, and behavioral phenotypes by other strategies, such as GWAS and mutation screening, including TCF4 (Pitt-Hopkins syndrome, intellectual disability, schizophrenia) (Amiel et al, 2007; Blake et al, 2010; Rosenfeld et al, 2009b), GRIN2B (schizophrenia, bipolar disorder, neurodevelopment) (Endele et al, 2010), EHMT1 (schizophrenia) (Kirov et al, 2012) and four novel neurodevelopmental genes that overlap with Category 3: ZNF804A (schizophrenia, psychosis, cognitive function) (O’Donovan et al, 2008; Walters et al, 2010), ANK3 (bipolar disorder, schizophrenia) (Ferreira et al, 2008; Williams et al, 2011), C18orf1 (schizophrenia) (Meerabux et al, 2009) and PDE10A (schizophrenia) (Kehler, 2011). All loci with the exception of ANK3 are supported by secondary CNV analyses (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Sequencing Chromosomal Abnormalities Reveals Neurodevelopmental Loci that Confer Risk across Diagnostic Boundaries

Talkowski

Rosenfeld

Blumenthal

et al. 2012

Cell

529

505

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SUMMARY Balanced chromosomal abnormalities (BCAs) represent a reservoir of single gene disruptions in neurodevelopmental disorders (NDD). We sequenced BCAs in autism and related NDDs, revealing disruption of 33 loci in four general categories: 1) genes associated with abnormal neurodevelopment (e.g., AUTS2, FOXP1, CDKL5), 2) single gene contributors to microdeletion syndromes (MBD5, SATB2, EHMT1, SNURF-SNRPN), 3) novel risk loci (e.g., CHD8, KIRREL3, ZNF507), and 4) genes associated with later onset psychiatric disorders (e.g., TCF4, ZNF804A, PDE10A, GRIN2B, ANK3). We also discovered profoundly increased burden of copy number variants among 19,556 neurodevelopmental cases compared to 13,991 controls (p = 2.07×10−47) and enrichment of polygenic risk alleles from autism and schizophrenia genome-wide association studies (p = 0.0018 and 0.0009, respectively). Our findings suggest a polygenic risk model of autism incorporating loci of strong effect and indicate that some neurodevelopmental genes are sensitive to perturbation by multiple mutational mechanisms, leading to variable phenotypic outcomes that manifest at different life stages.

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“…Three regions showing evidence of selection in the Swedish population are located on Chr 1 (24.0‐24.1, 24.4‐25.1, and 25.3‐25.9 Mb; 17 genes), each harboring several interesting candidate genes. The LDLRAD4 ( low‐density lipoprotein receptor class A domain containing 4) gene inhibits transforming growth factor‐β signaling 43 and is a putative schizophrenia‐related gene 44 . Another growth factor‐related gene in this region is CTGF (connective tissue growth factor).…”

Section: Resultsmentioning

confidence: 99%

Unravelling selection signatures in a single dog breed suggests recent selection for morphological and behavioral traits

et al. 2020

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Strong selection has resulted in substantial morphological and behavioral diversity across modern dog breeds, which makes dogs interesting model animals to study the underlying genetic architecture of these traits. However, results from between-breed analyses may confound selection signatures for behavior and morphological features that were coselected during breed development. In this study, we assess population genetic differences in a unique resource of dogs of the same breed but with systematic behavioral selection in only one population. We exploit these different breeding backgrounds to identify signatures of recent selection. Selection signatures within populations were found on chromosomes 4 and 19, with the strongest signals in behavior-related genes. Regions showing strong signals of divergent selection were located on chromosomes 1, 24, and 32, and include candidate genes for both physical features and behavior. Some of the selection signatures appear to be driven by loci associated with coat color (Chr 24; ASIP) and length (Chr 32; FGF5), while others showed evidence of association with behavior. Our findings suggest that signatures of selection within dog breeds have been driven by selection for morphology and behavior. Furthermore, we demonstrate that combining selection scans with association analyses is effective for dissecting the traits under selection.

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Analysis of a t(18;21)(p11.1;p11.1) translocation in a family with schizophrenia

Cited by 8 publications

References 23 publications

Genomic View of Bipolar Disorder Revealed by Whole Genome Sequencing in a Genetic Isolate

Genomic View of Bipolar Disorder Revealed by Whole Genome Sequencing in a Genetic Isolate

Sequencing Chromosomal Abnormalities Reveals Neurodevelopmental Loci that Confer Risk across Diagnostic Boundaries

Unravelling selection signatures in a single dog breed suggests recent selection for morphological and behavioral traits

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