It is a very exciting time to be in the field of human genetics. Since the sequencing of the human genome in 2003, genetics have tremendously improved the understanding of many human diseases, as well as nominated new targets for future therapies.
Dr. Mata's primary research goals are directed toward understanding the genetic component of neurological disorders, in particular Parkinson’s disease (PD), Parkinson’s Disease Dementia (PDD) and Dementia with Lewy Bodies (DLB). Most neurological disorders are very complex, both clinically and genetically, thus proposing a very interesting challenge. In most cases they are the result of a complex interaction between one’s genetics and the environment. Dr. Mata's lab uses approaches like case-control and family studies to identify those genetic risk factors that modify risk or cause the disease.
A significant focus of Dr. Mata's research has also been performing genetic studies in non-European populations, especially those with a minority ethnic background such as Latinos. For this Dr. Mata created and coordinated the Latin American Research consortium on the Genetics of PD (LARGE-PD), a collaboration of more than 12 institutions in many countries in Latin America. The reason behind it is that there is a tremendous lack of diversity in genetic research, with most large-genetic studies including only people of European ancestry, despite the fact that most diseases affect people from all genetic backgrounds. This is increasing the already existing health disparities in these populations.
The goal is to be able to apply this knowledge for a more precise treatment of all patients with neurological disorders.
In other words ...
Every person inherits information (genes) from their parents that determines characteristics like height, eye and hair or skin tone. But these genes also carry information that can protect or increase our chances of developing certain diseases. Dr. Mata's lab is working toward identifying and understanding the genes that play a role in those diseases that affect the brain (neurological disorders). These include the very well-known Parkinson’s disease (PD), but also other, less common, disorders, such as a form of PD that presents with severe cognitive problems/dementia (PDD) and another type of dementia called Dementia with Lewy Bodies (DLB). Identifying these genes is very important as they represent candidates for novel therapies that can help treat these disorders.
Dr. Mata's lab tries to include patients from all ethnicities in its studies, and is privileged to coordinate the Latin American Research consortium on the Genetics of PD (LARGE-PD). This consortium is trying to understand if these genetic factors are the same between populations or specific to certain populations. This inclusion of patients from all genetic backgrounds will be a key factor in developing genetic-based, personalized treatments.
Key Publications: (from newer to older)
Sarihan IE et al. Pre-Print
The overall identification of copy number variants (CNV) at a genome-wide level has been understudied in PD patients since most studies only screen a few known PD genes. Here we used genome-wide genotyping data from 747 PD patients and 632 ancestry matched controls from LARGE-PD to understand the genome-wide burden of copy number variants in Latinos and its association with disease:
Genome-wide copy number burden analysis showed no difference between patients vs. controls
Patients were significantly enriched for CNVs overlapping known PD genes (OR: 3.97 [1.69 - 10.5], P = 0.018), with PARK2 showing the strongest burden
Patients carrying a CNV in known PD genes present disease symptoms 26 years earlier compared to patients with CNVs in other genes
In Latin America 5.6% of Early-Onset PD patients carry a CNV in PARK2
Velez-Pardo C, Lorenzo-Betancor O, Jimenez-Del-Rio M, Moreno S, Lopera F, Cornejo-Olivas M, Torres L, Inca-Martinez M, Mazzetti P, Cosentino C, Yearout D, Waldherr SM, Zabetian CP, Mata IF. Parkinsonism Relat Disord. 2019 Jun;63:204-208. doi: 10.1016/j.parkreldis.2019.01.030. Epub 2019 Feb 4.
GBA is the most important risk factor for PD, however little is known about its effects in Latinos. Here we screened 602 PD patients and 319 controls from Colombia and Peru. The key findings were:
GBA is an important risk factor in this populations too, increase the risk to develop PD around 4.5 and 6.2 fold in Peru and Colombia respectively
While frequency in PD patients from Peru is similar to frequency in other countries (5.5%), frequency in Colombia is double (9.9%) due to the presence of a newly described population-specific mutation (p.K198E)
Mutations in GBA not only increase the risk to develop PD, but also advances the age at onset by about 8 years.
LARGE-PD: Examining the Genetics of Parkinson’s Disease in Latin America
Zabetial CP, Mata IF on behalf of the Latin American Research Consortium on the Genetics of PD (LARGE-PD). Mov Disord . 2017 Sep;32(9):1330-1331. doi: 10.1002/mds.27081. Epub 2017 Jun 28.
Mutations located in codons G2019 and R1441 of the leucine-rich repeat kinase 2 (LRRK2) gene represent the most common genetic cause of PD in patients of European origin.Here, we show that, in the LARGE-PD cohort, the combined frequency of these LRRK2 mutations varies substantially across countries in Latin America and is directly correlated with the estimated proportion of European ancestry at each site. This indicates that the genetic architecture of PD might differ between Latinos and other population groups, as it has been shown in several other diseases, including cancer.
Ignacio Mata, PhD, Genomic Medicine Institute, was recently awarded funding by The Michael J. Fox Foundation to continue his research on the genetics of Parkinson’s disease (PD) in Latino populations. The grant, which will provide nearly $740,000 over two years, is part of the largest initiative to expand genetic research to other countries in order to better define PD and discover new treatment options.
The identification of gene variants that cause or lead to Parkinson’s disease (PD) has revolutionized the medical research field by identifying novel targets for the development of precision treatments. However, the vast majority of these studies have been conducted in populations of European or Asian ancestry. No large-scale PD genetic studies have ever been conducted in Latino populations.