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Researchers Probe Chromosomal Abnormalities and their Role in Brain Disorders

Human chromosomes isolated from white blood cells. The red dots mark a matching piece of DNA that is normally found on chromosomes 1 ank 16.

In a biology classroom somewhere, students are looking at slides of dividing cells, learning about how the cells' chromosomes must be neatly lined up and sorted so that all the "daughter" cells end up with a full set. Sometimes, however, there are missteps in this dance of chromosomes, which are the structures that contain a cell's genes. Due to these missteps, a piece of one chromosome might be completely lost or inappropriately stitched onto another chromosome.

Often, these chromosomal rearrangements are very small and not easy to see by a student's untrained eye, but they can still have a large impact on health.

Photo of Dr. Lupski

With support through the NINDS Genetics and Genomics signature project, James Lupski, M.D., Ph.D., at Baylor College of Medicine in Houston is using state-of-the-art techniques to study chromosomal rearrangements, to better understand what causes them, and to investigate how they contribute to disease.

Chromosomal rearrangements are known to play a role in infertility, miscarriage, birth defects, and several rare neurological disorders. When a piece of chromosome becomes displaced, it carries its genes with it, leading to chromosomes that have extra copies or missing copies of some genes. Neurological disorders caused by these "copy number variations" include Charcot-Marie-Tooth disease type 1A (CMT1A), hereditary neuropathy with liability to pressure palsies (HNPP), and Prader-Willi syndrome.

In different individuals, these disorders can be traced to two different kinds of chromosomal rearrangements: typical (also called recurrent) or atypical (non-recurrent). This latter category is the focus of Dr. Lupski's research.

By way of example, most cases of CMT1A can be traced to typical rearrangements - the rearrangements look similar, occur at regular breakpoints (the places where a chromosome becomes fractured), and are caused by a known mechanism. Some individuals with CMT1A, however, have atypical rearrangements; in these cases, the exact locations of the breakpoints can differ and the underlying mechanisms are unclear. Interest in understanding atypical chromosomal rearrangements has grown, thanks to recent evidence that they might be risk factors for common disorders such as autism and schizophrenia.

Dr. Lupski and his team will use DNA sequencing and other methods to identify individuals with CMT1A and other disorders who have atypical chromosomal rearrangements. Then, they will precisely map the breakpoints and look for clues to causation. The ability to identify complex rearrangements - and to determine how they occur and what genes are affected - could lead to better diagnostic tests for neurological disorders and hint at new therapies.

The NINDS Genetics and Genomics signature project is funded through the American Recovery and Reinvestment Act (ARRA).

Photo caption: Human chromosomes isolated from white blood cells. The red dots mark a matching piece of DNA that is normally found on chromosomes 1 and 16. From Brunetti-Pierri et al., Nature Genetics, December 2008, vol. 40(12), p. 1466.

NINDS ( is the nation's primary supporter of biomedical research on the brain and nervous system.

 More information about NIH's ARRA grant funding opportunities can be found at To track the progress of HHS activities funded through the ARRA, visit To track all federal funds provided through the ARRA, visit

Last updated December 23, 2013