Monthly Archives: August 2017

August 2, 2017

Rare mutations in the amyloid precursor protein (APP) have previously been shown to be strongly associated with Alzheimer's disease (AD). Common genetic variants in this protein may also be linked to intelligence (IQ) in children, according to recent research performed at the University of Bergen, Norway.

Results of the research were published online today in the Journal of Alzheimer's Disease. Senior author Dr. Tetyana Zayats is a researcher at the KGJebsen Centre for Neuropsychiatric Disorders at the University of Bergen.

The study analyzed genetic markers and IQ collected from 5,165 children in the Avon Longitudinal Study of Parents and Children. The genetic findings were followed up in the genetic data from two adult datasets (1) 17,008 cases with AD and 37,154 controls, and (2) 112,151 individuals assessed for general cognitive functioning. The function of the genetic markers was analysed using reporter assays in cells.

Brain cells communicate via synapses containing hundreds of specialized proteins. Mutations in some of these proteins lead to dysfunctional synapses and brain diseases such as epilepsy, intellectual disability, autism or AD. Dr. Zayats and co-workers at the University of Bergen examined a subgroup of these proteins that have been implicated in synaptic plasticity and learning (the ARC complex). They found that a variation in DNA sequence within the gene encoding a member of this group of proteins, amyloid beta precursor protein (APP) was associated with non-verbal (fluid) intelligence in children, which reflects our capacity to reason and solve problems. In adults, this variation revealed association with AD, while the overall genetic variation within the APP gene itself appeared to be correlated with the efficiency of information processing (reaction time).

"This study has potential implications for our understanding of the normal function of these synaptic proteins as well as their involvement in disease" said Dr. Zayats.

APP encodes the amyloid- precursor protein that forms amyloid--containing neuritic plaques, the accumulation of which is one of the key pathological hallmarks in AD brains. However, it is unclear how these plaques affect brain functions and whether they lead to AD.

"Our understanding of biological processes underlying synaptic functioning could be expanded by examining human genetics throughout the lifespan as genetic influences may be the driving force behind the stability of our cognitive functioning," Dr. Zayats commented.

Genetic correlation between intelligence and AD has also been found in large-scale genome-wide analyses on general cognitive ability in adults. Several genes involved in general intelligence have previously reported to be associated with AD or related dementias. Such overlap has also been noted for the APP gene, where a coding variant was shown to be protective against both AD and cognitive decline in elderly.

"While this is only an exploratory study, in-depth functional and association follow up examinations are needed," Dr. Zayats noted. "Examining genetic overlap between cognitive functioning and AD in children - not only adults - presents us with a new avenue to further our understanding of the role of synaptic plasticity in cognitive functioning and disease."

Explore further: Overactive scavenger cells may cause neurodegeneration in Alzheimer's

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A protein involved in Alzheimer's disease may also be implicated in cognitive abilities in children - Medical Xpress

In collaboration with scientists from the U.K., Europe, Japan and the United States, researchers at the Human Genome Sequencing Center at Baylor College of Medicine have discovered a whole genome duplication during the evolution of spiders and scorpions. The study appears in BMC Biology.

Researchers have long been studying spiders and scorpions for both applied reasons, such as studying venom components for pharmaceuticals and silks for materials science, and for basic questions such as the reasons for the evolution and to understand the development and ecological success of this diverse group of carnivorous organisms.

As part of a pilot project for the i5K, a project to study the genomes of 5,000 arthropod species, the Human Genome Sequencing Center analyzed the genome of the house spider Parasteatoda tepidariorum a model species studied in laboratories and the Arizona bark scorpion Centruroides sculpturatus, the most venomous scorpion in North America.

Analysis of these genomes revealed that spiders and scorpions evolved from a shared ancestor more than 400 million years ago, which made new copies of all of the genes in its genome, a process called whole genome duplication. Such an event is one of the largest evolutionary changes that can happen to a genome and is relatively rare during animal evolution.

It is tremendously exciting to see rapid progress in our molecular understanding of a species that we coexist with on planet earth. Spider genome analysis is particularly tricky, and we believe this is one of the highest quality spider genomes to date, said Stephen Richards, associate professor in the Human Genome Sequencing Center, who led the genome sequencing at Baylor.

Similarly, there also have been two whole genome duplications at the origin of vertebrates, fuelling long-standing debate as to whether the duplicated genes enabled new biological complexity in the evolution of the vertebrate lineage leading to mammals. The new finding of a whole genome duplication in spiders and scorpions therefore provides a valuable comparison to the events in vertebrates and could help reveal genes and processes that have been important to our own evolution.

While most of the new genetic material generated by whole genome duplication is subsequently lost, some of the new gene copies can evolve new functions and may contribute to the diversification of shape, size, physiology and behavior of animals, said Alistair McGregor, professor of evolutionary developmental biology at Oxford Brookes University and lead author of the research. Comparing the whole genome duplication in spiders and scorpions with the independent events in vertebrates reveals a striking similarity. In both cases, duplicated clusters of Hox genes have been retained. These are very important genes that regulate development of body structures in all animals, and therefore can cause evolutionary changes in animal body plans.

The study also found that the copies of spider Hox genes show differences in when and where they are expressed, suggesting they have evolved new functions.

McGregor explains that these changes may help clarify the evolutionary innovations in spiders and scorpions including specialized limbs and how they breathe, as well as the production of different types of venom and silk, which spiders use to capture and kill their prey.

Many people fear spiders and scorpions, but this research shows what a beautiful part of the evolutionary tree they represent, said Richard Gibbs, director of the Human Genome Sequencing Center and the Wofford Cain Chair and professor of molecular and human genetics at Baylor.

Costs have now dropped rapidly enough from tens of millions of dollars to merely a few thousand dollars for this genomic analyses to now be performed on any species, Richards said. There is still so much more to learn about the life on earth around us, and I believe this result is just the beginning of understanding the molecular make up of spiders.

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Genome Sequencing Shows Spiders, Scorpions Share Ancestor - Laboratory Equipment