Genetic landscape of recessive diseases in the Vietnamese population from large-scale clinical exome sequencing.

Accurate profiling of population-specific recessive diseases is essential for the design of cost-effective carrier screening programs. However, minority populations and ethnic groups, including Vietnamese, are still underrepresented in existing genetic studies. Here, we reported the first comprehensive study of recessive diseases in the Vietnamese population. Clinical exome sequencing data of 4503 disease-associated genes obtained from a cohort of 985 Vietnamese individuals was analyzed to identify pathogenic variants, associated diseases and their carrier frequencies in the population. A total of 118 recessive diseases associated with 164 pathogenic or likely pathogenic variants were identified, among which 28 diseases had carrier frequencies of at least 1% (1 in 100 individuals). Three diseases were prevalent in the Vietnamese population with carrier frequencies of 2-12 times higher than in the world populations, including beta-thalassemia (1 in 23), citrin deficiency (1 in 31), and phenylketonuria (1 in 40). Seven novel pathogenic and two likely pathogenic variants associated with nine recessive diseases were discovered. The comprehensive profile of recessive diseases identified in this study enables the design of cost-effective carrier screening programs specific to the Vietnamese population.

Genetic profiling of Vietnamese population from large-scale genomic analysis of non-invasive prenatal testing data.

The under-representation of several ethnic groups in existing genetic databases and studies have undermined our understanding of the genetic variations and associated traits or diseases in many populations. Cost and technology limitations remain the challenges in performing large-scale genome sequencing projects in many developing countries, including Vietnam. As one of the most rapidly adopted genetic tests, non-invasive prenatal testing (NIPT) data offers an alternative untapped resource for genetic studies. Here we performed a large-scale genomic analysis of 2683 pregnant Vietnamese women using their NIPT data and identified a comprehensive set of 8,054,515 single-nucleotide polymorphisms, among which 8.2% were new to the Vietnamese population. Our study also revealed 24,487 disease-associated genetic variants and their allele frequency distribution, especially 5 pathogenic variants for prevalent genetic disorders in Vietnam. We also observed major discrepancies in the allele frequency distribution of disease-associated genetic variants between the Vietnamese and other populations, thus highlighting a need for genome-wide association studies dedicated to the Vietnamese population. The resulted database of Vietnamese genetic variants, their allele frequency distribution, and their associated diseases presents a valuable resource for future genetic studies.

Ultra-Deep Massive Parallel Sequencing of Plasma Cell-Free DNA Enables Large-Scale Profiling of Driver Mutations in Vietnamese Patients With Advanced Non-Small Cell Lung Cancer.

Population-specific profiling of mutations in cancer genes is of critical importance for the understanding of cancer biology in general as well as the establishment of optimal diagnostics and treatment guidelines for that particular population. Although genetic analysis of tumor tissue is often used to detect mutations in cancer genes, the invasiveness and limited accessibility hinders its application in large-scale population studies. Here, we used ultra-deep massive parallel sequencing of plasma cell free DNA (cfDNA) to identify the mutation profiles of 265 Vietnamese patients with advanced non-small cell lung cancer (NSCLC). Compared to a cohort of advanced NSCLC patients characterized by sequencing of tissue samples, cfDNA genomic testing, despite lower mutation detection rates, was able to detect major mutations in tested driver genes that reflected similar mutation composition and distribution pattern, as well as major associations between mutation prevalence and clinical features. In conclusion, ultra-deep sequencing of plasma cfDNA represents an alternative approach for population-wide genetic profiling of cancer genes where recruitment of patients is limited to the accessibility of tumor tissue site.

Effect of the edible mushroom Mycoleptodonoides aitchisonii on transient global ischemia-induced monoamine metabolism changes in rat cerebral cortex.

We performed a transient bilateral common carotid artery occlusion on rats and investigated whether feeding an aqueous extract of Mycoleptodonoides aitchisonii, an edible mushroom, affected metabolism of monoamines in the cerebral cortex, possibly protecting against ischemic damage. Seventeen days after the surgery, concentrations of the dopamine (DA) metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) and of homovanillic acid (HVA) in the cerebral cortex of the M. aitchisonii-fed group (MV) were higher than in the control ischemia (CV) group. The turnover rate of DA, which was indicated by (DOPAC+HVA)/DA, for the CV group was significantly lower than for the MV group, and the MV group value was the same rate as the sham-operated group. These data indicate that M. aitchisonii affects the dopaminergic neuronal system following brain ischemia damage in the cerebral cortex.

Mycoleptodonoides aitchisonii affects brain nerve growth factor concentration in newborn rats.

Fourteen days pregnant Wistar strain rats were fed powder or aqueous extract of the edible fungus MycoleptFodonoides aitchisonii. Nerve growth factor (NGF) concentrations were measured in the brain of newborn rats during the lactation period at 0, 7 and 14 days after the birth. Two M. aitchisonii-fed groups showed a significant increase in NGF concentrations in brain halves compared to those who were fed control feed at days 7 and 14. At day 21, NGF concentrations in the cerebral cortex and hippocampus were not significantly different among the three groups. After weaning, the young rats were fed the same test diet as their mothers. Ten days later, Morris water maze test was started. After the test, the rats were sacrificed and NGF concentrations in the cerebral cortex and hippocampus were measured. Significant NGF concentration increases were detected in the cerebral cortex for two M. aitchisonii-fed groups and in the hippocampus in the aqueous extract group. These results suggest that NGF in the brain reached the same levels by day 21, but that M. aitchisonii affected the growth rate in the lactation period. The learning test stimulated the brain and some compounds of M. aitchisonii enhanced NGF synthesis in rat cerebral cortex and hippocampus.