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Non-coding variation in disorders of sex development

(2017) CLINICAL GENETICS. 91(2). p.163-172
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Abstract
Genetic studies in Disorders of Sex Development (DSD), representing a wide spectrum of developmental or functional conditions of the gonad, have mainly been oriented towards the coding genome. Application of genomic technologies, such as whole-exome sequencing, result in a molecular genetic diagnosis in similar to 50% of cases with DSD. Many of the genes mutated in DSD encode transcription factors such as SRY, SOX9, NR5A1, and FOXL2, characterized by a strictly regulated spatiotemporal expression. Hence, it can be hypothesized that at least part of the missing genetic variation in DSD can be explained by non-coding mutations in regulatory elements that alter gene expression, either by reduced, mis-or overexpression of their target genes. In addition, structural variations such as translocations, deletions, duplications or inversions can affect the normal chromatin conformation by different mechanisms. Here, we review non-coding defects in human DSD phenotypes and in animal models. The wide variety of non-coding defects found in DSD emphasizes that the regulatory landscape of known and to be discovered DSD genes has to be taken into consideration when investigating the molecular pathogenesis of DSD.
Keywords
CNVs, DSD, gene regulation, non-coding variation, ACAMPOMELIC CAMPOMELIC DYSPLASIA, GENOTYPE-PHENOTYPE CORRELATION, REGULATORY REGION UPSTREAM, TESTIS-DETERMINING GENE, ANDROGEN RECEPTOR GENE, PIERRE-ROBIN-SEQUENCE, KB DELETION UPSTREAM, SRY-RELATED GENE, TRANSLOCATION BREAKPOINTS, RECIPROCAL TRANSLOCATION

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Chicago
Baetens, Dorien, Berenice Bilharinho de Mendonça, Hannah Verdin, Martine Cools, and Elfride De Baere. 2017. “Non-coding Variation in Disorders of Sex Development.” Clinical Genetics 91 (2): 163–172.
APA
Baetens, Dorien, Bilharinho de Mendonça, B., Verdin, H., Cools, M., & De Baere, E. (2017). Non-coding variation in disorders of sex development. CLINICAL GENETICS, 91(2), 163–172.
Vancouver
1.
Baetens D, Bilharinho de Mendonça B, Verdin H, Cools M, De Baere E. Non-coding variation in disorders of sex development. CLINICAL GENETICS. 2017;91(2):163–72.
MLA
Baetens, Dorien, Berenice Bilharinho de Mendonça, Hannah Verdin, et al. “Non-coding Variation in Disorders of Sex Development.” CLINICAL GENETICS 91.2 (2017): 163–172. Print.
@article{8507711,
  abstract     = {Genetic studies in Disorders of Sex Development (DSD), representing a wide spectrum of developmental or functional conditions of the gonad, have mainly been oriented towards the coding genome. Application of genomic technologies, such as whole-exome sequencing, result in a molecular genetic diagnosis in similar to 50\% of cases with DSD. Many of the genes mutated in DSD encode transcription factors such as SRY, SOX9, NR5A1, and FOXL2, characterized by a strictly regulated spatiotemporal expression. Hence, it can be hypothesized that at least part of the missing genetic variation in DSD can be explained by non-coding mutations in regulatory elements that alter gene expression, either by reduced, mis-or overexpression of their target genes. In addition, structural variations such as translocations, deletions, duplications or inversions can affect the normal chromatin conformation by different mechanisms. Here, we review non-coding defects in human DSD phenotypes and in animal models. The wide variety of non-coding defects found in DSD emphasizes that the regulatory landscape of known and to be discovered DSD genes has to be taken into consideration when investigating the molecular pathogenesis of DSD.},
  author       = {Baetens, Dorien and Bilharinho de Mendon\c{c}a, Berenice and Verdin, Hannah and Cools, Martine and De Baere, Elfride},
  issn         = {0009-9163},
  journal      = {CLINICAL GENETICS},
  keyword      = {CNVs,DSD,gene regulation,non-coding variation,ACAMPOMELIC CAMPOMELIC DYSPLASIA,GENOTYPE-PHENOTYPE CORRELATION,REGULATORY REGION UPSTREAM,TESTIS-DETERMINING GENE,ANDROGEN RECEPTOR GENE,PIERRE-ROBIN-SEQUENCE,KB DELETION UPSTREAM,SRY-RELATED GENE,TRANSLOCATION BREAKPOINTS,RECIPROCAL TRANSLOCATION},
  language     = {eng},
  number       = {2},
  pages        = {163--172},
  title        = {Non-coding variation in disorders of sex development},
  url          = {http://dx.doi.org/10.1111/cge.12911},
  volume       = {91},
  year         = {2017},
}

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