SMAD4 mutations causing Myhre syndrome are under positive selection in the male germline.

While it is widely thought that de novo mutations (DNMs) occur randomly, we previously showed that some DNMs are enriched because they are positively selected in the testes of aging men. These "selfish" mutations cause disorders with a shared presentation of features, including exclusive paternal origin, significant increase of the father's age, and high apparent germline mutation rate. To date, all known selfish mutations cluster within the components of the RTK-RAS-MAPK signaling pathway, a critical modulator of testicular homeostasis.

High-dose AraC is essential for the treatment of ML-DS independent of postinduction MRD: results of the COG AAML1531 trial.

Myeloid leukemia in children with Down syndrome (ML-DS) is associated with young age and somatic GATA1 mutations. Because of high event-free survival (EFS) and hypersensitivity of the leukemic blasts to chemotherapy, the prior Children's Oncology Group protocol ML-DS protocol (AAML0431) reduced overall treatment intensity but lacking risk stratification, retained the high-dose cytarabine course (HD-AraC), which was highly associated with infectious morbidity. Despite high EFS of ML-DS, survival for those who relapse is rare.

Humanized zebrafish enhance human hematopoietic stem cell survival and promote acute myeloid leukemia clonal diversity.

Xenograft models are invaluable tools in establishing the current paradigms of hematopoiesis and leukemogenesis. The zebrafish has emerged as a robust alternative xenograft model but, like mice, lack specific cytokines that mimic the microenvironment found in human patients. To address this critical gap, we generated the first humanized zebrafish that express human hematopoietic-specific cytokines (GM-CSF, SCF, and SDF1α).

Clonal hematopoiesis and risk of acute myeloid leukemia.

Nearly all adults harbor acute myeloid leukemia (AML)-related clonal hematopoietic mutations at a variant allele fraction (VAF) of ≥0.0001, yet relatively few develop hematologic malignancies. We conducted a nested analysis in the Nurses' Health Study and Health Professionals Follow-Up Study blood subcohorts, with up to 22 years of follow up to investigate associations of clonal mutations of ≥0.

Distal chromosome 16p11.2 duplications containing in patients with scoliosis.

Introduction: Adolescent idiopathic scoliosis (AIS) is a common musculoskeletal disorder with strong evidence for a genetic contribution. CNVs play an important role in congenital scoliosis, but their role in idiopathic scoliosis has been largely unexplored.

Methods: Exome sequence data from 1197 AIS cases and 1664 in-house controls was analysed using coverage data to identify rare CNVs.

Rare Event Detection Using Error-corrected DNA and RNA Sequencing.

Conventional next-generation sequencing techniques (NGS) have allowed for immense genomic characterization for over a decade. Specifically, NGS has been used to analyze the spectrum of clonal mutations in malignancy. Though far more efficient than traditional Sanger methods, NGS struggles with identifying rare clonal and subclonal mutations due to its high error rate of ~0.

Associations between dietary habits and risk factors for cardiovascular diseases in a Hong Kong Chinese working population--the "Better Health for Better Hong Kong" (BHBHK) health promotion campaign.

Diet and nutritional status have been shown to play pivotal roles in the occurrence of many chronic diseases. In this study, we examined the patterns of dietary habits and their relationships with risk factors for cardiovascular and chronic diseases in Hong Kong working populations. In April 2000, a 5-year territory-wide health promotion campaign supported by the Li Ka Shing Foundation was launched in Hong Kong by the Health InfoWorld of Hospital Authority.

Low levels of awareness of suboptimal health conditions in a high-risk working population: the "better health for better Hong Kong" health promotion campaign.

The incidences of cardiovascular risk factors such as obesity and diabetes are rising in many Asian populations. In April 2000, a 5-year territory-wide health promotion campaign supported by Li Ka Shing Foundation was launched in Hong Kong by the Health InfoWorld of Hospital Authority. From the general working class, 4,832 Chinese people were randomly recruited into this campaign.

Doubling over ten years of central obesity in Hong Kong Chinese working men.

Background: Obesity is now an epidemic in most parts of the world. In this cross sectional study, we report the most recent data on obesity in Hong Kong Chinese working population and compare the changes over 10 years.

Methods: Between July 2000 and March 2002, 5882 adult subjects from the working class in Hong Kong were recruited (2716 men (46.