Nuytemans Karen, Rajabli Farid, Bussies Parker L, Celis Katrina, Scott William K, Singer Carlos, Luca Corneliu C, Vinuela Angel, Pericak-Vance Margaret A, Vance Jeff M
John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States.
Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, United States.
Front Neurol. 2020 Nov 12;11:573733. doi: 10.3389/fneur.2020.573733. eCollection 2020.
The Latino population is greatly understudied in biomedical research, including genetics. Very little information is available on presence of known variants originally identified in non-Hispanic white patients or novel variants in the Latino population. The Latino population is admixed, with contributions of European, African, and Amerindian ancestries. Therefore, the ancestry surrounding a gene (local ancestry, LA) can be any of the three contributing ancestries and thus can determine the presence or risk effect of variants detected. We sequenced the major exons and exons of reported Latino-specific variants in and and performed genome-wide genotyping for LA assessments in 79 Latino Parkinson disease (PD) patients, of which ~80% identified as Caribbean Latino. We observed five carriers of LRRK2 p.G2019S, one GBA p.T408M, and three GBA p.N409S on European as well as three GBA p.L13R on African LA backgrounds. Previous Latino variant GBA p.K237E was not observed in this dataset. A novel highly conserved and predicted damaging variant LRRK2 p.D734N was identified in two unrelated individuals with African LA. Additionally, we identified rare, functional variants LRRK2 p.P1480L and GBA p.S310G in one individual each heterozygous for European/Amerindian LA. Additional functional analysis will be needed to determine the pathogenicity of the novel variants in PD. However, the identification of novel disease variants in the Latino cohort potentially contributing to PD supports to importance of inclusion of Latinos in genetics research to provide insight in PD genetics in Latinos specifically as well as other populations with the same ancestral contributions.
拉丁裔人群在包括遗传学在内的生物医学研究中受到的关注极少。关于最初在非西班牙裔白人患者中发现的已知变异或拉丁裔人群中的新型变异的信息非常有限。拉丁裔人群是混合血统，有欧洲、非洲和美洲印第安人的血统贡献。因此，基因周围的血统（本地血统，LA）可以是三种贡献血统中的任何一种，从而可以决定检测到的变异的存在或风险效应。我们对[具体文献]中报道的拉丁裔特异性变异的主要外显子和外显子进行了测序，并对79名拉丁裔帕金森病（PD）患者进行了全基因组基因分型以评估LA，其中约80%被确定为加勒比拉丁裔。我们在欧洲血统背景上观察到5名携带LRRK2 p.G2019S的个体、1名携带GBA p.T408M的个体和3名携带GBA p.N409S的个体，以及在非洲血统背景上观察到3名携带GBA p.L13R的个体。在该数据集中未观察到先前报道的拉丁裔变异GBA p.K237E。在两名具有非洲血统的不相关个体中发现了一种新的高度保守且预测具有有害性的变异LRRK2 p.D734N。此外，我们在一名欧洲/美洲印第安血统杂合的个体中分别鉴定出罕见的功能性变异LRRK2 p.P1480L和GBA p.S310G。需要进行额外的功能分析来确定这些新变异在帕金森病中的致病性。然而，在拉丁裔队列中鉴定出可能导致帕金森病的新疾病变异，支持了将拉丁裔纳入遗传学研究的重要性，以便专门深入了解拉丁裔以及其他具有相同祖先贡献人群的帕金森病遗传学。
