Professor of Biomedical Informatics, Harvard Medical School
Professor of Medicine, Brigham and Women’s Hospital
Dr. Sunyaev
is a computational genomicist and geneticist. Research in his lab encompasses
many aspects of population genetic variation including the origin of mutations,
the effect of allelic variants on molecular function, population and
evolutionary genetics, and genetics of human complex and Mendelian traits. He
developed several computational and statistical methods widely adopted by the
community.
Dr. Sunyaev
obtained a PhD in molecular biophysics from the Moscow Institute of Physics and
Technology and completed his postdoctoral training in bioinformatics at the
European Molecular Biology Laboratory (EMBL). He is an Associate Member at
Broad Institute of MIT and Harvard. He co-leads the NHGRI-funded Genome
Sequencing Program Analysis Center and is actively involved in the Undiagnosed
Diseases Network and in the Brigham Genomic Medicine program. He also
co-organizes the Boston Evolutionary Genomics Group.
Professor of Biomedical Informatics, Harvard Medical School
Professor of Medicine, Brigham and Women’s Hospital
Dr. Sunyaev
is a computational genomicist and geneticist. Research in his lab encompasses
many aspects of population genetic variation including the origin of mutations,
the effect of allelic variants on molecular function, population and
evolutionary genetics, and genetics of human complex and Mendelian traits. He
developed several computational and statistical methods widely adopted by the
community.
Dr. Sunyaev
obtained a PhD in molecular biophysics from the Moscow Institute of Physics and
Technology and completed his postdoctoral training in bioinformatics at the
European Molecular Biology Laboratory (EMBL). He is an Associate Member at
Broad Institute of MIT and Harvard. He co-leads the NHGRI-funded Genome
Sequencing Program Analysis Center and is actively involved in the Undiagnosed
Diseases Network and in the Brigham Genomic Medicine program. He also
co-organizes the Boston Evolutionary Genomics Group.
Journal article
CONCLUSIONS: Specific variants in the tankyrase-binding domain of AXIN2 are pathogenic, leading to phenotypic expansion with potential context-dependent effects on AXIN2 function and Wnt signaling. The N1 modeling strategy used to demonstrate variant pathogenicity may be beneficial for resolving other heterozygous variants associated with congenital anomalies.
Journal article
CONCLUSION: This case supports the pathogenicity of the DNASE1L3 p.Ile60Ser variant broadening the genetic spectrum. Plasma DNA fragment analysis provides a sensitive biomarker of impaired nuclease function, and JAK inhibition may offer partial therapeutic benefit in DNASE1L3-related systemic inflammation.