Study finds origin of inherited gene mutation causing early-onset Alzheimer's

December 4, 2013
(A-D) This shows geographic origin of the haplotype spanning E280 A. Credit: UCSB

The age and origin of the E280A gene mutation responsible for early-onset Alzheimer's in a Colombian family with an unusually high incidence of the disease has been traced to a single founder dating from the 16th century.

Kenneth S. Kosik, Harriman Professor in Neuroscience at UC Santa Barbara and co-director of the campus's Neuroscience Research Institute (NRI), conducted the study. The findings appear in the journal Alzheimer's & Dementia.

"Some mutations just increase your risk, but this mutation is not a risk," Kosik said. "This mutation is highly penetrant, which means that if you carry the mutation, you will get early-onset Alzheimer's disease."

Kosik's team sequenced the genomes of more than 100 and applied identity-by-descent analysis to identify regions of common ancestry. DNA is inherited from both the parents and recombined in chunks. From these pieces, scientists can identify which parent —and sometimes which grandparent or great-grandparent—is the source of the DNA. As time goes by, sections of DNA recombine into smaller and smaller segments, each representing a history of its ancestry.

Sequencing the genomes came about because the researchers knew that while most family members with the mutation develop early-onset Alzheimer's at age 45, there were a small number of outliers. "A few people got it a decade later, a few got it a decade earlier and we wondered if there was a gene that was protecting those who got the disease later," Kosik explained. "That protective gene—even though this mutation exists only in this Colombian family —might be useful for all of us. That research is still ongoing."

All carriers of E280 A share a minimal common haplotype spanning 1.8 Mb surrounding presenilin 1 E280 A from rs2158987 to rs10135303 (chromosome 14). Positions are given in GRCh37 coordinates. Credit: UCSB

Out of the genome sequencing came the idea of determining where the originated. In addition to DNA analysis, the researchers conducted interviews with the older healthy individuals of each affected family and spoke to genealogists and historians in Colombia's Antioquian region. Kosik's co-author Francisco Lopera examined local historical and genealogical books, last wills and ecclesiastical records dating as far back as 1540.

When the scientists examined the DNA patterns around the gene mutation site, they found markers from the Iberian peninsula. They estimated the age and geographic origin of E280A to be consistent with a single founder dating from the time of the Spanish Conquistadors who began colonizing Colombia during the early 16th century.

"This doesn't have big medical implications, but it shows that genetics is a very powerful tool and can be used to reconstruct history," Kosik said. "What we've done here might be called 'neuroarchaeology.' "

Explore further: Clinical trials for Alzheimer's drug to begin in early 2013

Related Stories

Clinical trials for Alzheimer's drug to begin in early 2013

May 22, 2012
After an announcement by federal officials approving clinical trials for the drug Crenezumab, researchers searching for a way to treat Alzheimer's Disease are gearing up for a rare study that will allow them to test a therapy ...

Same genes linked to early- and late-onset Alzheimer's disease

February 1, 2012
The same gene mutations linked to inherited, early-onset Alzheimer's disease have been found in people with the more common late-onset form of the illness.

New risk gene discovery gives hope to early-onset breast cancer sufferers

October 24, 2013
A new breast cancer risk gene has been discovered which explains the early-onset breast cancer in some multiple-case breast cancer families.

RNA build-up linked to dementia and motor neuron disease

October 30, 2013
A new toxic entity associated with genetically inherited forms of dementia and motor neuron disease has been identified by scientists at the UCL Institute of Neurology. The toxin is the result of a genetic mutation that leads ...

Rare genomic mutations found in 10 families with early-onset, familial Alzheimer's disease

June 17, 2013
Although a family history of Alzheimer's disease is a primary risk factor for the devastating neurological disorder, mutations in only three genes – the amyloid precursor protein and presenilins 1 and 2 – have been established ...

Recommended for you

Scientists provide insight into genetic basis of neuropsychiatric disorders

July 21, 2017
A study by scientists at the Children's Medical Center Research Institute at UT Southwestern (CRI) is providing insight into the genetic basis of neuropsychiatric disorders. In this research, the first mouse model of a mutation ...

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Late-breaking mutations may play an important role in autism

July 17, 2017
A study of nearly 6,000 families, combining three genetic sequencing technologies, finds that mutations that occur after conception play an important role in autism. A team led by investigators at Boston Children's Hospital ...

Newly discovered gene variants link innate immunity and Alzheimer's disease

July 17, 2017
Three new gene variants, found in a genome wide association study of Alzheimer's disease (AD), point to the brain's immune cells in the onset of the disorder. These genes encode three proteins that are found in microglia, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.