A5090317029- Genomic variations and chromosomal abnormalities
- Prenatal Screening and Diagnostics
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Chromosomal and Genetic Variations
- Sexual Differentiation and Disorders
- Congenital heart defects research
- Acute Myeloid Leukemia Research
- Genomics and Rare Diseases
- Renal and related cancers
- Genetics and Neurodevelopmental Disorders
- Urological Disorders and Treatments
- Sarcoma Diagnosis and Treatment
- RNA modifications and cancer
- Reproductive Biology and Fertility
- DNA Repair Mechanisms
- Chronic Lymphocytic Leukemia Research
- Assisted Reproductive Technology and Twin Pregnancy
- Genomics and Chromatin Dynamics
- Genetic Syndromes and Imprinting
- Genetic factors in colorectal cancer
- Fetal and Pediatric Neurological Disorders
- Congenital Anomalies and Fetal Surgery
- RNA regulation and disease
- Tumors and Oncological Cases
- BRCA gene mutations in cancer
Stanford University
2024-2025
University of Pittsburgh
2015-2024
UPMC Health System
2024
Magee-Womens Research Institute
2015-2024
University of Pittsburgh Medical Center
2014-2024
Stanford Medicine
2024
Magee-Womens Hospital
2014-2023
GTx (United States)
2022
The University of Texas MD Anderson Cancer Center
2022
Brigham and Women's Hospital
2022
The genetic basis of nonobstructive azoospermia is unknown in the majority infertile men.We performed array comparative genomic hybridization testing blood samples obtained from 15 patients with azoospermia, and we mutation screening by means direct Sanger sequencing testis-expressed 11 gene (TEX11) open reading frame semen 289 384 controls.We identified a 99-kb hemizygous loss on chromosome Xq13.2 that involved three TEX11 exons. This loss, which was identical 2 predicts deletion 79 amino...
Premature ovarian failure (POF) is a genetically and phenotypically heterogeneous disorder that includes individuals with manifestations ranging from primary amenorrhea to loss of menstrual function prior age 40. POF presents as hypergonadotropic hypogonadism can be part syndrome or occur in isolation. Here, we studied 3 sisters amenorrhea, hypothyroidism, hypogonadism. The were born parents who are first cousins. SNP analysis whole-exome sequencing revealed the presence pathogenic variant...
PurposeWe developed a microarray for clinical diagnosis of chromosomal disorders using large insert genomic DNA clones as targets comparative hybridization (CGH).MethodsThe array contains 362 FISH-verified that span regions implicated in over 40 known human and representative subtelomeric each the 41 clinically relevant chromosome telomeres. Three or four from almost all deletion duplication three more region were included. We tested analysis (CMA) masked fashion by examining 25 patients who...
Meiosis is unique to germ cells and essential for reproduction. During the first meiotic division, homologous chromosomes pair, recombine, form chiasmata. The homologues connect via axial elements numerous transverse filaments synaptonemal complex. complex a critical component chromosome pairing, segregation, recombination. We previously identified novel cell–specific HORMA domain encoding gene, Hormad1, member of mammalian counterpart yeast protein Hop1. Hormad1 gametogenesis as knockout...
Background Array Comparative Genomic Hybridization (a-CGH) is a powerful molecular cytogenetic tool to detect genomic imbalances and study disease mechanism pathogenesis. We report our experience with the clinical implementation of this high resolution human genome analysis, referred as Chromosomal Microarray Analysis (CMA). Methods Findings CMA was performed clinically on 2513 postnatal samples from patients variety phenotypes. The initial 775 were studied using array version 4 remaining...
Disorders of sexual development (DSD), ranging in severity from genital abnormalities to complete sex reversal, are among the most common human birth defects with incidence rates reaching almost 3%. Although causative alterations key genes controlling gonad have been identified, majority DSD cases remain unexplained. To improve diagnosis, we screened 116 children born idiopathic using a clinically validated array-based comparative genomic hybridization platform. 8951 controls without...
Uterine leiomyomas are benign tumors that can cause pain, bleeding, and infertility in some women. Mediator complex subunit 12 (MED12) exon 2 variants associated with uterine leiomyomas; however, the causality of MED12 variants, their genetic mode action, role genomic instability have not been established. Here, we generated a mouse model conditionally expresses Med12 missense variant (c.131G>A) uterus demonstrated this alteration alone promotes leiomyoma formation hyperplasia both WT mice...
Significance Sex development involves a precise spatiotemporal expression and interactions of numerous genetic factors, including the WT1 (Wilms tumor 1) gene. Complete partial loss-of-function variants are associated with 46,XY disorders/differences sex (DSD). Some 46,XX individuals develop testis in absence testis-determining gene SRY . We describe genotype/phenotype association where impacting C-terminal zinc finger (ZF4) cause individuals. XX mice carrying pathogenic variant ZF4 display...
Abstract Subtelomeric imbalances are a significant cause of congenital disorders. Screening for these abnormalities has traditionally utilized GTG‐banding analysis, fluorescence in situ hybridization (FISH) assays, and multiplex ligation‐dependent probe amplification. Microarray‐based comparative genomic (array‐CGH) is relatively new technology that can identify microscopic submicroscopic chromosomal imbalances. It been proposed an array with extended coverage at subtelomeric regions could...
SOX8 is an HMG-box transcription factor closely related to SRY and SOX9. Deletion of the gene encoding Sox8 in mice causes reproductive dysfunction but role humans unknown. Here, we show that expressed somatic cells early developing gonad human influences sex determination. We identified two individuals with 46, XY disorders/differences development (DSD) chromosomal rearrangements encompassing locus a third individual DSD missense mutation SOX8. In vitro functional assays indicate this...
Neurodevelopmental disorders are impairments of brain function that affect emotion, learning, and memory. Copy number variations contactin genes (CNTNs), including CNTN3, CNTN4, CNTN5, CNTN6, have been suggested to be associated with these disorders. However, phenotypes reported in only a handful patients copy involving CNTNs. From January 2009 2013, 3724 ascertained through the University Pittsburgh Medical Center were referred our laboratory for clinical array comparative genomic...
Abstract Considerable evidence suggests that breast cancer therapeutic resistance and relapse can be driven by polyploid giant cells (PGCCs). The number of PGCCs increases with the stages disease stress. Given importance PGCCs, it remains challenging to eradicate them. To discover effective anti-PGCC compounds, there is an unmet need rapidly distinguish compounds kill non-PGCCs, or both. Here, we establish a single-cell morphological analysis pipeline high throughput great precision...
Abstract Purpose Miscarriage, often resulting from a variety of genetic factors, is common pregnancy outcome. Preconception carrier screening (PGCS) identifies at-risk partners for newborn disorders; however, PGCS panels currently lack miscarriage-related genes. In this study, we evaluated the potential impact both known and candidate genes on prenatal lethality effectiveness in diverse populations. Methods We analyzed 125,748 human exome sequences mouse gene function databases. Our goals...
We characterized at the molecular level genomic rearrangements in 28 unrelated patients with 9q34.3 subtelomeric deletions. Four distinct categories were delineated: terminal deletions, interstitial derivative chromosomes and complex rearrangements; each results haploinsufficiency of EHMT1 gene a characteristic phenotype. Interestingly, 25% our had de novo found only 50% bona fide In contrast to disorders that are often associated recurrent rearrangements, breakpoints involving subtelomere...
Inactivating FSH receptor (FSHR) mutations can affect ovarian function, resulting in variable clinical presentations ranging from primary amenorrhea to premature menopause. FSHR have been largely reported the Finnish population, but patients of Asian Indian descent, incidence is extremely rare.Two female siblings descent were diagnosed with failure and hypergonadotropic hypogonadism. The daughters result a consanguineous marriage between second cousins. A combination comparative genomic...
Background Copy number variants (CNVs) contribute to 3% 10% of isolated congenital heart disease (CHD) cases, yet their pathogenic roles remain unclear. Diagnostic efforts have focused on protein‐coding genes, largely overlooking long noncoding RNAs (lncRNAs), which play key in development and disease. Methods AND RESULTS We systematically analyzed lncRNAs overlapping clinically validated CNVs 743 patients with CHD from the Cytogenomics Cardiovascular Malformations Consortium. identified...