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Somatic mutations in autism spectrum disorder

Award Number: K08MH136407
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 12/30/2025
PERIOD OF PERFORMANCE END DATE: 06/30/2028

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Somatic mutations in autism spectrum disorder - PROJECT SUMMARY / ABSTRACT This NIH K08 proposal describes a four-year career development training program in autism spectrum disorder (ASD) genomics research. With this research program, Dr. Mo will develop expertise in human genetics, analysis of next-generation sequencing data, and interpretation of somatic variants in non-neoplastic tissue. These skills complement Dr. Mo’s prior research and clinical training and ideally position her to transition to an independent investigator position studying somatic mutations in ASD. Dr. Mo’s mentor for this proposal is Dr. Christopher A. Walsh, a Professor of Neurology at Harvard Medical School, an HHMI Investigator at Boston Children’s Hospital, and a leader in the genetics of human neurological diseases. With over 25 years of mentorship experience, Dr. Walsh has an established track record of mentoring trainees to successful academic careers in biomedical research. Dr. Mo will be supported by a scientific advisory team and collaborators with complementary expertise in autism genetics, computational genomics, genotype-phenotype correlations of somatic mutations, and career mentorship. The institutional resources available at Boston Children’s Hospital, which is affiliated with Harvard Medical School, are world- class and provide an ideal environment to foster the development of a physician-scientist career. The primary scientific objective of the proposed research plan is to study the role of somatic (post- zygotic) variants in ASD. Dr. Mo’s central hypothesis is that somatic variants contribute to ASD risk. Dr. Mo provides pilot data indicating that somatic single nucleotide variants (sSNVs) are increased in gene exons in ASD probands compared to controls, particularly in highly constrained genes with loss-of-function intolerance. Furthermore, Dr. Mo shows that sSNVs in non-coding gene regulatory regions can be efficiently detected using ATAC-seq, which allows the detection of non-coding sSNVs in larger sample sizes than previously possible using whole genome sequencing. To achieve the research objective, a combination of whole exome sequencing, ATAC-seq, whole genome sequencing, amplicon sequencing, and computational analysis will be used. These strategies will systemically examine two independent, but related, aims: (1) the burden of sSNVs in functionally-relevant genes in ASD compared to neurotypical individuals; and (2) the distribution of sSNVs in non-coding gene regulatory regions in postmortem human brain neurons from ASD and neurotypical individuals. Findings from this study may improve our understanding of the genetic architecture and mechanisms of ASD as well as the genetic diagnosis of ASD in clinical practice.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2025	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Mental Health Research Grants	003	3	3/5/2026	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$7,074
2026	2025	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Mental Health Research Grants	002	2	3/5/2026	NON-COMPETING CONTINUATION	$7,074
2026	2025	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Mental Health Research Grants	001	3	1/30/2026	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$188,298
2026	2025	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Mental Health Research Grants	000	2	1/30/2026	NON-COMPETING CONTINUATION	-$188,298
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $194,940 )
2025	2025	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Mental Health Research Grants	000	2	6/18/2025	NON-COMPETING CONTINUATION	$194,940
														Subtotal = $194,940

Issue Date FY: 2024 ( Subtotal = $194,940 )
2024	2024	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Mental Health Research Grants	000	1	5/13/2024	NEW	$194,940
														Subtotal = $194,940

Grand Total All Awards = $389,880

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Somatic mutations in autism spectrum disorder

Award Number: K08MH136407

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 12/30/2025

PERIOD OF PERFORMANCE END DATE: 06/30/2028

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