GUILHERME LOPES YAMAMOTO
Projetos de Pesquisa
Unidades Organizacionais
Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina
3 resultados
Resultados de Busca
Agora exibindo 1 - 3 de 3
- Whole-genome sequencing of 1,171 elderly admixed individuals from Sao Paulo, Brazil(2022) NASLAVSKY, Michel S.; SCLIAR, Marilia O.; YAMAMOTO, Guilherme L.; WANG, Jaqueline Yu Ting; ZVERINOVA, Stepanka; KARP, Tatiana; NUNES, Kelly; CERONI, Jose Ricardo Magliocco; CARVALHO, Diego Lima de; SIMOES, Carlos Eduardo da Silva; BOZOKLIAN, Daniel; NONAKA, Ricardo; SILVA, Nayane dos Santos Brito; SOUZA, Andreia da Silva; ANDRADE, Heloisa de Souza; PASSOS, Marilia Rodrigues Silva; CASTRO, Camila Ferreira Bannwart; MENDES-JUNIOR, Celso T.; V, Rafael L. Mercuri; MILLER, Thiago L. A.; BUZZO, Jose Leonel; REGO, Fernanda O.; ARAUJO, Nathalia M.; MAGALHAES, Wagner C. S.; MINGRONI-NETTO, Regina Celia; BORDA, Victor; GUIO, Heinner; ROJAS, Carlos P.; SANCHEZ, Cesar; CACERES, Omar; DEAN, Michael; BARRETO, Mauricio L.; LIMA-COSTA, Maria Fernanda; HORTA, Bernardo L.; TARAZONA-SANTOS, Eduardo; MEYER, Diogo; GALANTE, Pedro A. F.; GURYEV, Victor; CASTELLI, Erick C.; DUARTE, Yeda A. O.; PASSOS-BUENO, Maria Rita; ZATZ, MayanaAs whole-genome sequencing (WGS) becomes the gold standard tool for studying population genomics and medical applications, data on diverse non-European and admixed individuals are still scarce. Here, we present a high-coverage WGS dataset of 1,171 highly admixed elderly Brazilians from a census-based cohort, providing over 76 million variants, of which similar to 2 million are absent from large public databases. WGS enables identification of similar to 2,000 previously undescribed mobile element insertions without previous description, nearly 5 Mb of genomic segments absent from the human genome reference, and over 140 alleles from HLA genes absent from public resources. We reclassify and curate pathogenicity assertions for nearly four hundred variants in genes associated with dominantly-inherited Mendelian disorders and calculate the incidence for selected recessive disorders, demonstrating the clinical usefulness of the present study. Finally, we observe that whole-genome and HLA imputation could be significantly improved compared to available datasets since rare variation represents the largest proportion of input from WGS. These results demonstrate that even smaller sample sizes of underrepresented populations bring relevant data for genomic studies, especially when exploring analyses allowed only by WGS.
- Vertebral segmentation defects in a Brazilian cohort: Clinical and molecular analysis focused on spondylocostal dysostosis(2022) LINNENKAMP, Bianca; GIRARDI, Raissa; ROCHA, Leticia; YAMAMOTO, Guilherme; CERONI, Jose Ricardo; MENDES, Antonia Elisabeth Cristhina; HONJO, Rachel; OLIVEIRA, Luiz Antonio; AMEMIYA, Raphael Bruno; QUAIO, Caio; OLIVEIRA FILHO, Joao Bosco de; KIM, Chong Ae; BERTOLA, Debora
- The recurrent homozygous translation start site variant in CCDC134 in an individual with severe osteogenesis imperfecta of non-Morrocan ancestry(2022) ALI, Taccyanna M.; LINNENKAMP, Bianca D. W.; YAMAMOTO, Guilherme L.; HONJO, Rachel S.; MENEZES FILHO, Hamilton Cabral de; KIM, Chong Ae; BERTOLA, Debora R.Osteogenesis imperfecta (OI) is a rare low-bone mass skeletal Mendelian disorder characterized by bone fragility leading to bone fractures, with deformities and stunted growth in the more severe phenotypes. Other common, nonskeletal findings include blue sclerae and dentinogenesis imperfecta. It is caused mainly by quantitative or structural defects in type I collagen, although dysregulation of different signaling pathways that play a role in bone morphogenesis has been described to be associated with a small fraction of individuals with OI. Recently, a homozygous variant in the translation start site of CCDC134, showing increased activation of the RAS/MAPK signaling pathway, has been reported in three families of Moroccan origin with a severe, deforming form of OI. We report on a 9-year-old Brazilian boy, harboring the same homozygous variant in CCDC134, also presenting severe bone involvement. This report contributes to the phenotypic delineation of this novel autosomal recessive form of OI, which presents with high prevalence of nonunion fractures considered rare events in OI in general. In addition, it expands the phenotype to include base skull anomalies, potentially leading to serious complications, as seen in severe forms of OI. A poor response to bisphosphonate therapy was observed in these individuals. As the variant in CCDC134 leads to dysregulation of the RAS/MAPK signaling pathway, drugs targeted to this pathway could be an alternative to achieve a better management of these individuals.