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Background: Although glucose‐6‐phosphate dehydrogenase (G6PD) deficiency is the most common inherited disorder in the Chinese population, there is scarce evidence regarding the epidemiology, evolutionary origin, and malaria‐induced positive selection effects of G6PD‐deficient alleles in various Chinese ethnic populations. Methods: We performed a large population‐based screening (n = 15,690) to examine the impact of selection on human nucleotide diversity and to infer the evolutionary history of the most common deficiency alleles in Chinese populations. Results: The frequencies of G6PD deficiency ranged from 0% to 11.6% in 12 Chinese ethnic populations. A frequency map based on geographic information showed that G6PD deficiency was highly correlated with historical malaria prevalence in China and was affected by altitude and latitude. The five most frequently occurring G6PD gene variants were NM_001042351.3:c.1376G>T, NM_001042351.3:c.1388G>A, NM_001042351.3:c.95A>G, NM_001042351.3:c.1311T>C, and NM_001042351.3:c.1024C>T, which were distributed with ethnic features. A pathogenic but rarely reported variant site (NM_001042351.3:c.448G>A) was identified in this study. Bioinformatic analysis revealed a strong and recent positive selection targeting the NM_001042351.3:c.1376G>T allele that originated in the past 3125 to 3750 years and another selection targeting the NM_001042351.3:c.1388G>A allele that originated in the past 5000 to 6000 years. Additionally, both alleles originated from a single ancestor. Conclusion: These results indicate that malaria has had a major impact on the Chinese genome since the introduction of rice agriculture. [ABSTRACT FROM AUTHOR]

Tooth agenesis is the most common developmental dental anomaly. Absence of one or two permanent teeth is found in the majority of affected subjects. Very few patients suffer severe tooth agenesis. Recent studies revealed that WNT10A gene mutations caused syndromic and isolated severe tooth agenesis. In this study, to determine the contribution of WNT10A variants in different severities of tooth agenesis, we investigated the association between WNT10A variants and non-syndromic tooth agenesis in a Chinese population consisting of 505 tooth agenesis patients and 451 normal controls. Twenty-three novel non-synonymous variants were identified. WNT10A variants were detected in 15.8 % (75/474) of patients with 1-3 missing teeth and 51.6 % (16/31) of patients with 4 or more missing teeth. As compared with a frequency of 3.1 % in individuals with full dentition, variant allele frequencies were significantly elevated in both groups with tooth agenesis ( p values of 1.00 × 10 and 3.89 × 10, respectively). Our findings showed that WNT10A variants were associated with non-syndromic tooth agenesis from mild to severe tooth agenesis, and the more severe tooth agenesis, the stronger association. Biallelic genotypes of WNT10A variants may have a pathogenic effect on tooth development. Presence of a single variant allele would be predisposing for causation with low penetrance. Together with WNT10A variant, there should be other genetic or environmental factors leading to biallelic variant-related variable clinical manifestations and single allele variant-related low penetrance. The frequent missing tooth positions in the WNT10A-related cases were consistent with that in the general population, suggesting WNT10A plays a critically important role in the etiology of general tooth agenesis. [ABSTRACT FROM AUTHOR]