To capture the full spectrum of genetic risk for autism, we performed a two-stage analysis of rare de novo and inherited coding variants in 42,607 autism cases, including 35,130 new cases recruited online by SPARK. We identified 60 genes with exome-wide significance (P < 2.5 × 10−6), including five new risk genes (NAV3, ITSN1, MARK2, SCAF1 and HNRNPUL2). The association of NAV3 with autism risk is primarily driven by rare inherited loss-of-function (LoF) variants, with an estimated relative risk of 4, consistent with moderate effect. Autistic individuals with LoF variants in the four moderate-risk genes (NAV3, ITSN1, SCAF1 and HNRNPUL2; n = 95) have less cognitive impairment than 129 autistic individuals with LoF variants in highly penetrant genes (CHD8, SCN2A, ADNP, FOXP1 and SHANK3) (59% vs 88%, P = 1.9 × 10−6). Power calculations suggest that much larger numbers of autism cases are needed to identify additional moderate-risk genes.
Despite the known heritable nature of autism spectrum disorder (ASD), studies have primarily identified risk genes with de novo variants (DNVs). To capture the full spectrum of ASD genetic risk, we performed a two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases recruited online by SPARK. In the first stage, we analyzed 19,843 cases with one or both biological parents and found that known ASD or neurodevelopmental disorder (NDD) risk genes explain nearly 70% of the genetic burden conferred by DNVs. In contrast, less than 20% of genetic risk conferred by rare inherited loss-of-function (LoF) variants are explained by known ASD/NDD genes. We selected 404 genes based on the first stage of analysis and performed a meta-analysis with an additional 22,764 cases and 236,000 population controls. We identified 60 genes with exome-wide significance (p < 2.5e-6), including five new risk genes (NAV3, ITSN1, MARK2, SCAF1, and HNRNPUL2). The association of NAV3 with ASD risk is entirely driven by rare inherited LoFs variants, with an average relative risk of 4, consistent with moderate effect. ASD individuals with LoF variants in the four moderate risk genes (NAV3, ITSN1, SCAF1, and HNRNPUL2, n = 95) have less cognitive impairment compared to 129 ASD individuals with LoF variants in well-established, highly penetrant ASD risk genes (CHD8, SCN2A, ADNP, FOXP1, SHANK3) (59% vs. 88%, p= 1.9e-06) . These findings will guide future gene discovery efforts and suggest that much larger numbers of ASD cases and controls are needed to identify additional genes that confer moderate risk of ASD through rare, inherited variants.
BackgroundCrop genetic resources are important components of biodiversity. However, with the large-scale promotion of mono-cropping, genetic diversity has largely been lost. Ex-situ conservation approaches were widely used to protect traditional crop varieties worldwide. However, this method fails to maintain the dynamic evolutionary processes of crop genetic resources in their original habitats, leading to genetic diversity reduction and even loss of the capacity of resistance to new diseases and pests. Therefore, on-farm conservation has been considered a crucial complement to ex-situ conservation. This study aimed at clarifying the genetic diversity differences between ex-situ conservation and on-farm conservation and to exploring the influence of traditional cultures on genetic diversity of rice landraces under on-farm conservation.MethodsThe conservation status of rice landrace varieties, including Indica and Japonica, non-glutinous rice (Oryza sativa) and glutinous rice (Oryza sativa var. glutinosa Matsum), was obtained through ethno-biology investigation method in 12 villages of ethnic groups from Guizhou, Yunnan and Guangxi provinces of China. The genetic diversity between 24 pairs of the same rice landraces from different times were compared using simple sequence repeat (SSR) molecular markers technology. The landrace paris studied were collected in 1980 and maintained ex-situ, while 2014 samples were collected on-farm in southwest of China.ResultsThe results showed that many varieties of rice landraces have been preserved on-farm by local farmers for hundreds or thousands of years. The number of alleles (Na), effective number of alleles (Ne), Nei genetic diversity index (He) and Shannon information index (I) of rice landraces were significantly higher by 12.3–30.4 % under on-farm conservation than under ex-situ conservation. Compared with the ex-situ conservation approach, rice landraces under on-farm conservation programs had more alleles and higher genetic diversity. In every site we investigated, ethnic traditional cultures play a positive influence on rice landrace variety diversity and genetic diversity.ConclusionMost China’s rice landraces were conserved in the ethnic areas of southwest China. On-farm conservation can effectively promote the allelic variation and increase the genetic diversity of rice landraces over the past 35 years. Moreover, ethnic traditional culture practices are a crucial foundation to increase genetic diversity of rice landraces and implement on-farm conservation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13002-016-0120-0) contains supplementary material, which is available to authorized users.
BackgroundKam Sweet Rice (KSR) is a special kind of rice landrace that has been cultivated for thousands of years in the borders of Guizhou, Hunan, and Guangxi Provinces of China, and is mainly distributed in southeast Guizhou Province of China currently. KSR has many unique qualities, including strong resistance to diseases, pests, and adverse abiotic conditions, difficulty of threshing, and well glutinous features. KSR germplasm resources are an indispensable material and cultural symbol in the production and daily life and customs of the Dong people. Related studies showed that numerous traditional KSR varieties and cultivation area of KSR decreased sharply from the Qing dynasty to 2015, but many KSR varieties are still conserved in Dong villages of southeast Guizhou Province compared to other areas. However, the number of KSR varieties that are conserved on farms in southeast Guizhou Province and factors influencing the erosion and conservation of KSR genetic resources is unclear. Therefore, this study was an on-farm conservation investigation of KSR genetic resource in China’s major KSR producing areas—Liping, Congjiang, and Rongjiang counties in Guizhou Province and influencing factors analysis of KSR abandonment and conservation.MethodsThe information of KSR conservation status and variety characteristics, typical villages, Dong’s cultural customs, and factors influencing KSR abandonment and conservation was obtained using ethno-biology methods, mainly through field research interviews, including participatory observation, semi-structured interviews, key informant interviews, focus group discussions, and cultural anthropology. The altitude, plant height, awn color and length, hull color, and rice color of 156 KSR accessions in 28 villages were recorded. The variety quantity and cultivation area of KSR were investigated in 33 ethnic villages. Questionnaire surveys were conducted in typical Dong villages to obtain local farmers’ attitudes toward cultivation and protection of KSR. We randomly selected 26 farmers from Sizhai village and 30 farmers from Huanggang village and chose 3 social characteristics including age, gender, and education levels of farmers, and adopted the method of face-to-face interviewing to complete the questionnaires. Then, we analyzed the correlation and determined the significance between farmers with different social characteristics and farmers’ attitudes to KSR development and protection using SPSS 17.0 software.Results(1) On-farm conservation status of KSR: a total of 156 KSR varieties were collected from 28 ethnic minority villages from 13 townships (accounting for 21% of three counties) in Liping, Congjiang, and Rongjiang counties. KSR accessions accounted for more than 90% of local rice varieties in each village. According to local farmers, although the quantity of KSR varieties decreased more than 50% in the investigated villages compared to the past 10–20 years, some Dong villages have still cultivated KSR, accounting for more than 50% of the rice field area in 10 villages. Th...
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