Page 116 - Genomic Medicine in Emerging Economies

Introduction 105

hundreds of years of admixture and is composed of variable rates of Caucasian,
African, and Native American genes, there is a weak correlation with skin color
(Parra et al., 2003). Even in global consortia data, Native American ancestry
is usually underrepresented (and consequently not deeply investigated) in
comparison with Caucasians, which comprise the majority of the worldwide
genetic consortia (such as Hapmap or the 1000 Genomes initiatives) (Sudmant
et al., 2015). High levels of Native American ancestry may have an impact on
the genetic basis of NPG in the continent (De Castro and Restrepo, 2015). A
recent international initiative, the Exome Aggregation Consortium, analyzed
the data for about 60,000 exomes, including more than 5000 exomes from
Latin American individuals (mainly from Mexico) (Lek et al., 2016).
The particular features of the genetic and environmental background of Latin
American populations are known to be correlated with different risks for
human diseases (including NPD) and endophenotypes; this also applies to the
response of pharmacological treatments (Adhikari et al., 2016; Suarez-Kurtz
and Pena, 2006). As an example of environmental factors for NPDs in Latin
America, in the 2004 Pelotas Birth Cohort Study, children from low-income
families had a higher prevalence of any mental disorder, especially for atten-
tion-deficit/hyperactivity disorder (ADHD), than those from wealthy families
(14% vs. 8%) (Santos et al., 2014). In the same cohort, the authors evaluated
the prevalence of intellectual disabilities, observing a high frequency of envi-
ronmental causes, which underscored the importance of early interventions
for children so as to minimize the impact of NPDs (Karam et al., 2016).

Advances in Molecular Genetics of Neurological Diseases in
Latin America
Considering that genetic factors play an important role in the susceptibility to
neurological disorders (Zoghbi and Warren, 2010), several studies have analyzed
candidate genes for NDs in samples from Latin American countries (Table 6.2). As
non-Mendelian forms of NDs represent the large majority of cases, several stud-
ies have explored polymorphisms in candidate genes (such as APOE, COMT, and
TOMM40, among others) that might be associated with NDs in Latin American
countries, such as Alzheimer’s disease, stroke, and Parkinson’s disease (Arboleda
et al., 2001; Benitez et al., 2010; Camelo et al., 2004; Forero et al., 2006a,b; Isordia-
Salas et al., 2010; Pereira et al., 2012; Vieira et al., 2016). For ADHD, several genes
(such as SNAP25, SLC6A3, and GRM7) have been studied (Akutagava-Martins
et al., 2014a,b; Bruxel et al., 2016; Castro et al., 2013; Cupertino et al., 2017; de
Azeredo et al., 2014; Fonseca et al., 2015; Gálvez et al., 2014; Genro et al., 2007;
Guimaraes et al., 2009a; Guimaraes et al., 2007; Kortmann et al., 2013; Mar-
tínez-levy et al., 2013; Mota et al., 2015; Roman et al., 2003; Salatino-Oliveira
et al., 2012a; Salatino-Oliveira et al., 2015; Tovo-Rodrigues et al., 2012). Other
studies have analyzed mutations in causal genes (such as PSEN1, PSEN2, and