| Full text | |
| Author(s): Show less - |
Costa, Claudia I. Samogy
;
Campos, Gabriele da Silva
;
Montenegro, Eduarda Morgana da Silva
;
Wang, Jaqueline Yu Ting
;
Scliar, Marilia
;
Monfardini, Frederico
;
Zachi, Elaine Cristina
;
Lourenco, Naila C. V.
;
Chan, Ada J. S.
;
Pereira, Sergio L.
;
Engchuan, Worrawat
;
Thiruvahindrapuram, Bhooma
;
Zarrei, Mehdi
;
Scherer, Stephen W.
;
Passos-Bueno, Maria Rita
Total Authors: 15
|
| Document type: | Journal article |
| Source: | European Journal of Human Genetics; v. 31, n. 9, p. 6-pg., 2023-06-06. |
| Abstract | |
De novo variants (DNVs) analysis has proven to be a powerful approach to gene discovery in Autism Spectrum Disorder (ASD), which has not yet been shown in a Brazilian ASD cohort. The relevance of inherited rare variants has also been suggested, particularly in oligogenic models. We hypothesized that three-generation analyses of DNVs could provide new insights into the relevance of de novo and inherited variants across generations. To accomplish this goal, we performed whole-exome sequencing of 33 septet families composed of probands, parents, and grandparents (n = 231 individuals) and compared DNV rates (DNVr) between generations and those from two control cohorts. The DNVr in the probands (DNVr = 1.16) was marginally higher than in parents (DNVr = 0.60; p = 0.054), and in controls (DNVr = 0.68; p = 0.035, congenital heart disorder and DNVr = 0.70; p = 0.047, unaffected ASD siblings from Simons Simplex Collection). Moreover, most of the DNVs were found to have paternal origin in both generations (84.6%). Finally, we observed that 40% (6/15) of the DNVs in parents transmitted for probands are in ASD or ASD candidate genes, representing recently emerged risk variants to ASD in their families and suggest ZNF536, MSL2 and HDAC9 as ASD candidate genes. We did not observe an enrichment of risk variants nor sex bias of transmitted variants in the three generations, that can be due to sample size. These results further reinforce the relevance of de novo variants in ASD. (AU) | |
| FAPESP's process: | 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center |
| Grantee: | Mayana Zatz |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 18/13743-5 - Big data analysis of genomic variants in ASD individuals and validation of new candidate genes |
| Grantee: | Eduarda Morgana da Silva Montenegro Malaguti de Souza |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate |
| FAPESP's process: | 17/05824-2 - Investigation of parents de novo risk variants in Autism Spectrum Disorder (ASD) |
| Grantee: | Eduarda Morgana da Silva Montenegro Malaguti de Souza |
| Support Opportunities: | Scholarships in Brazil - Doctorate |