The HGG Advances Award for Outstanding Early Career Publication recognizes research excellence from ASHG members who have recently begun their independent research careers. Philip Boone, a clinical geneticist, former postdoc, and now an Instructor in the lab, was awarded this for his paper on SMC3 mutations in HGG Advances at the 2024 ASHG conference in [...]
The current standard of care for fetal genetic testing requires an invasive medical procedure such as amniocentesis to survey individual DNA changes in the fetal genome. Here, the Talkowski laboratory has developed a new technology that enables pregnant persons to screen the protein-coding sequence of all genes in the fetal genome from a simple blood [...]
In a recent paper published in the American Journal of Human Genetics, postdoctoral research fellow Chelsea Lowther and graduate student Elise Valkanas co-led a large-scale study to systematically evaluate genome sequencing as a single test to displace the sequential application of karyotype, chromosomal microarray, and exome sequencing for the diagnostic assessment of autism spectrum disorder [...]
Autism spectrum disorder (ASD) is a developmental disorder that affects social interactions and communication. Scientists have discovered that changes in the function of certain proteins due to genetic variations can contribute to the risk of developing ASD. However, understanding how all these genes work together has been challenging. In this study, we analyzed samples from [...]
The structural variations (SVs) in the non-coding region of 5q14.3 near a gene called MEF2C — a transcription factor, has been linked to neurodevelopmental disorders (NDDs). The paper, published in the American Journal of Human Genetics, is the first to describe the long-range effects of coding and non-coding MEF2C variants in human iPSCs derived neuronal [...]
In this study, we conducted in-depth analyses to evaluate the power of different sequencing technologies, including long-read and short-read whole genome sequencing (WGS), in discovering genomic structural variation (SV). Our study revealed that albeit the over two-fold increase in the power of SV discovery by long-read sequences when compared against short reads, vast majority of [...]
Recurrent and reciprocal copy number variations (CNVs) pose a substantial risk for neurodevelopmental and neuropsychiatric disorders. One example of such CNVs is recurrent deletion and duplication of an ~ 743 kb genomic segment of chromosome 16p11.2, which consists of an ~ 593 kb unique segment encompassing 27 protein-coding genes and an ~ 150 kb flanking [...]
Large copy number variants (CNVs)—deletions or duplications of more than 100,000 DNA nucleotides—are collectively one of the strongest risk factors for abnormal neurodevelopment. However, interpreting CNVs in clinical genetic practice is challenging due to the lack of standardized resources for predicting the impact of CNVs on individual genes. By harmonizing and jointly analyzing genetic data [...]
Leveraging genetic sequencing data of the protein-coding portion of the human genome from more than 60,000 individuals, we found 72 genes to be associated with autism spectrum disorder (ASD) at a stringent threshold of less than 0.1% false discovery rate (FDR). The bulk of the evidence for these implicated genes were contributed by de [...]
X-linked Dystonia-Parkinsonism (XDP), is a rare Mendelian disorder predominantly observed on Panay island in the Philippines. The clinical phenotype most frequently combines features of dystonia and parkinsonism in a characteristic temporal progression. A region of the X-chromosome was linked to the disorder, yet the pathogenic mechanism has remained elusive. We demonstrate that this disorder is [...]
