Elaine T. Lim
A5085118026- Autism Spectrum Disorder Research
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Single-cell and spatial transcriptomics
- CRISPR and Genetic Engineering
- Genetics and Neurodevelopmental Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer Genomics and Diagnostics
- Genetic Associations and Epidemiology
- Bioinformatics and Genomic Networks
- Congenital heart defects research
- RNA modifications and cancer
- Pluripotent Stem Cells Research
- Epigenetics and DNA Methylation
- Multiple Sclerosis Research Studies
- Alzheimer's disease research and treatments
- Mitochondrial Function and Pathology
- RNA regulation and disease
- Cancer-related gene regulation
- Renal Transplantation Outcomes and Treatments
- Peripheral Neuropathies and Disorders
- interferon and immune responses
- Cellular transport and secretion
- Herpesvirus Infections and Treatments
- Amyotrophic Lateral Sclerosis Research
University of Massachusetts Chan Medical School
2020-2024
Harvard University
2014-2024
NeuroNexus (United States)
2022-2024
Boston Children's Hospital
2014-2023
Howard Hughes Medical Institute
2014-2023
Harvard University Press
2023
Boston VA Research Institute
2021
Broad Institute
2012-2020
UMass Memorial Medical Center
2020
Massachusetts Institute of Technology
2012-2015
Exome sequencing studies in complex diseases are challenged by the allelic heterogeneity, large number and modest effect sizes of associated variants on disease risk presence numbers neutral variants, even phenotypically relevant genes. Isolated populations with recent bottlenecks offer advantages for studying rare as they have deleterious that present at higher frequencies well a substantial reduction variation. To explore potential Finnish founder population low-frequency (0.5–5%)...
De novo mutations affect risk for many diseases and disorders, especially those with early-onset. An example is autism spectrum disorders (ASD). Four recent whole-exome sequencing (WES) studies of ASD families revealed a handful novel genes, based on independent de loss-of-function (LoF) falling in the same gene, found that LoF occurred at twofold higher rate than expected by chance. However successful these were, they used only small fraction data, excluding other types inherited rare...
The combination of ataxia and hypogonadism was first described more than a century ago, but its genetic basis has remained elusive.We performed whole-exome sequencing in patient with hypogonadotropic hypogonadism, followed by targeted candidate genes similarly affected patients. Neurologic reproductive endocrine phenotypes were characterized detail. effects sequence variants the presence an epistatic interaction tested zebrafish model.Digenic homozygous mutations RNF216 OTUD4, which encode...
The molecular basis of the earliest neuronal changes that lead to Alzheimer's disease (AD) is unclear. Here, we analyze neural cells derived from sporadic AD (SAD), APOE4 gene-edited and control induced pluripotent stem (iPSCs). We observe major differences in iPSC-derived progenitor (NP) neurons gene networks related differentiation, neurogenesis, synaptic transmission. SAD patients exhibit accelerated differentiation reduced cell renewal. Moreover, a similar phenotype appears NP cerebral...
Incorporating TLR9-inhibitory sequences in the AAV vector genome inhibits immunogenicity and enhances transgene expression multiple animal models.
Although autism has a clear genetic component, the high heterogeneity of disorder been challenge for identification causative genes. We used homozygosity analysis to identify probands from nonconsanguineous families that showed evidence distant shared ancestry, suggesting potentially recessive mutations. Whole-exome sequencing 16 revealed validated homozygous, pathogenic mutations segregated perfectly with disease in 4/16 families. The candidate genes (UBE3B, CLTCL1, NCKAP5L, ZNF18) encode...
Congenital diarrheal disorders (CDDs) are a collection of rare, heterogeneous enteropathies with early onset and often severe outcomes. Here, we report family Ashkenazi Jewish descent, 2 out 3 children affected by CDD. Both presented days after birth severe, intractable diarrhea. One child died from complications at age 17 months. The second showed marked improvement, resolution most symptoms 10 to 12 months age. Using exome sequencing, identified rare splice site mutation in the DGAT1 gene...
We report on results from whole-exome sequencing (WES) of 1,039 subjects diagnosed with autism spectrum disorders (ASD) and 870 controls selected the NIMH repository to be similar ancestry cases. The WES data came two centers using different methods produce sequence call variants it. Therefore, an initial goal was ensure distribution rare variation for centers. This proved straightforward by filtering called fraction missing data, read depth, balance alternative reference reads. Results were...
Endosomal sorting complex required for transport (ESCRT) proteins regulate biogenesis and release of extracellular vesicles (EVs), which enable cell-to-cell communication in the nervous system essential development adult function. We recently showed human loss-of-function (LOF) mutations ESCRT-III member CHMP1A cause autosomal recessive microcephaly with pontocerebellar hypoplasia, but its mechanism was unclear. Here, we show Chmp1a is progenitor proliferation mouse cortex cerebellum...