• Our Objective:

    • To identify apparently balanced chromosomal rearrangements in patients with multiple congenital anomalies and then to use these chromosomal rearrangements to map and identify genes that are disrupted or dysregulated in critical stages of human development.

  • Project Highlights:
  • Describing sequencing results of structural chromosome rearrangements with a suggested next-generation cytogenetic nomenclature.


    Am J Hum Genet 2014; 94:695-709.

    With recent rapid advances in genomic technologies, precise delineation of structural chromosome rearrangements at the nucleotide level is becoming increasingly feasible. In this era of "next-generation cytogenetics" (i.e., an integration of traditional cytogenetic techniques and next-generation sequencing), a consensus nomenclature is essential for accurate communication and data sharing. Currently, nomenclature for describing the sequencing data of these aberrations is lacking. Herein, we present a system called Next-Gen Cytogenetic Nomenclature, which is concordant with the International System for Human Cytogenetic Nomenclature (2013). This system starts with the alignment of rearrangement sequences by BLAT or BLAST (alignment tools) and arrives at a concise and detailed description of chromosomal changes. To facilitate usage and implementation of this nomenclature, we are developing a program designated BLA(S)T Output Sequence Tool of Nomenclature (BOSToN), a demonstrative version of which is accessible online. A standardized characterization of structural chromosomal rearrangements is essential both for research analyses and for application in the clinical setting.

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    Haploinsufficiency of KDM6A is associated with severe psychomotor retardation, global growth restriction, seizures and cleft palate


    Hum Genet 2013; 132:537–552.

    Histone methylation, a dynamic process regulated by methyltransferases and demethylases, has been identified as an epigenetic mechanism that plays an important role in regulation of global and tissue-specific gene expression at precise developmental stages.  KDM6A, a histone 3 lysine 27 demethylase and a histone 3 lysine 4 methyl-transferase, was disrupted and dysregulated in a female with severe and diverse structural defects and developmental abnormalities and a 46,X,t(X;5)(p11.3;q35.3)inv(5)(q35.3q35.1)dn.  This study illuminates the complex human phenotype resulting from abnormal KDM6A dosage. This study was selected for Faculty 1000 Genomics and Genetics. Faculty 1000 highlights and evaluates the most interesting and scientifically meritorious papers published in the biological sciences, based on the recommendations of over 5000 of the world's top researchers.

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    Disruption of MBD5 contributes to a spectrum of psychopathology and neurodevelopmental abnormalities


    Mol Psychiatry. 2013; [epub ahead of print].

    The impact of MBD5 disruption on neurodevelopment was reported by DGAP investigators and colleagues in Am J Hum Genet 2011 Oct 7;89(4):551-63.  In this paper, the role of MBD5 in a spectrum of additional human neuropsychiatric phenotypes is identified, ranging from early childhood developmental anomalies to psychopathology to behavioral regression and early onset dementia, further annotating the morbid human genome and the consequences of disruption of this dosage sensitive locus in the genome.

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