| Biography: Dr. Fabienne Wavrant-De Vrieze is a human geneticist whose research interests focus on the genetics of neurological disease. Dr. Wavrant-De Vrieze received her B.Sc. and Ph.D. from the University of Lille, France where she investigated the discovery of new genetic factor contributing to Alzheimer's disease. Dr. Wavrant-De Vrieze performed her postdoctoral training at the Mayo Clinic in Jacksonville, Florida, studying the genetic basis of neurological diseases such as Alzheimer and Guam's disease. In 2003, she joined the NIA as a Facility Head within the newly created Laboratory of Neurogenetics. Dr. Wavrant-De Vrieze's group is helping to seek the genetic causes of diverse neurological diseases. |
| Overview: Neurodegenerative diseases are complex diseases with diverse forms of transmission within the same pathology. Indeed, disorders such as Alzheimer and Parkinson's diseases can present as rare familial forms as well as more common "sporadic" forms. Consequently, the study of the genetic causes of these diseases is difficult. The two most common approaches that are being used are association and linkage studies. The first is based on the investigation of candidate genes chosen according to their biological function. By studying the segregation of their genotype and the transmission of the disease, genetic variation can be implicated in the disease. The second kind of study uses genetic markers that are spread out through the whole genome. Statistical analysis allows us to identify which markers are likely to be located near a gene that is involved in the development of the disease. |
| The main goal of our group is to discover loci that have genes that could potentially be involved in the development of diverse pathology, and then to study their association with disease. We are studying several forms of dementia, as well as other forms of neurodegenerative diseases and neurodevelopmental disorder. Currently, we are performing 3 genome screens in collaboration with colleagues from the NIH as well as with other groups. |
| The last stage of the genome screen being performed on siblings affected by the late-onset form of Alzheimer's disease (AD) will soon provide us with clues about which chromosomal region to focus on, in order to identify the gene(s) that contribute to this pathology. To date, only 1 gene has been identified as a risk factor for late-onset AD, the apolipoprotein E. Currently, several genes are being studied to establish if they are linked to AD. Those genes were chosen according to their position on chromosomal loci that were suggested to be inked to disease. Those chromosomal regions are sizeable, and they contain a large number of genes. By refining the genome screen and adding more samples to the population being studied, we hope to narrow down these genetic regions and ultimately identify the genetic variation contributing to disease. |
| The two other genome screens are being performed on samples that present neurodevelopmental diseases. Our collaborations with Drs. Judith Rapoport, NIMH, NIH, and Maximilian Muenke, NHGRI, NIH, consists of a 10cM genome screen on families that are affected by the childhood-onset form of schizophrenia (COS) in the first case, while the pathology that we are investigating in the second case is the Holoprosencephaly (HPE). |
| It is believed that COS is a disease which causes abnormal maturation of certain brain structures precipitated by multiple genetic defects. Cytogenetic abnormalities, which are due to changes in autosomes and sex chromosomes, have been found to be related to COS. Although twin and adoption studies have shown that genetics has an influence on the cause of COS, the level and nature of this effect is unclear (Kendler and Diehl, 1993). Although it's unclear whether schizophrenia has a single cause or multiple underlying causes, evidence suggests that it is a pathology likely involving a genetic predisposition, a prenatal insult to the developing brain and stressful life events. The role of genetics has long been established; the risk of schizophrenia rises from 1 percent with no family history of the illness, to 10 percent if a first degree relative has it, to 50 percent if an identical twin has it. But, it has not yet been determined which specific genes cause the brain abnormalities related to COS. |
| HPE is a disorder in which the fetal brain does not grow forward and divide as it is supposed to during early pregnancy. It is a birth defect that occurs during the first few weeks of intrauterine life. Although many children with HPE have normal chromosomes, specific chromosomal abnormalities have been identified in some patients. There is evidence that in some families, HPE is inherited (autosomal dominant as well as autosomal or X-linked recessive inheritance). Several genes have already been identified that play a role in holoprosencephaly. Indeed, to date, four genes have been identified that cause HPE in some families, but changes in these genes are found in only 10-20% of patients with HPE. Thus, more progress will be needed to understand the causes of HPE in the remaining families. |
