Nav: Home

New insights into human genetic variation revealed: Nature paper

August 17, 2016

Published in today's edition of Nature, the research led by Dr Monkol Lek of the University of Sydney and Dr Daniel MacArthur of The Broad Institute of MIT and Harvard Universities reveals patterns of genetic variation worldwide by sequencing the exomes of 60,706 individuals with diverse geographic ancestries, including European, African, South Asian, East Asian and Latino populations.

Using a massive exome sequencing database made available through the Exome Aggregation Consortium (ExAC), the international research team identified around 7.4 million genetic variants, providing unprecedented resolution into low-frequency protein-coding variants in human populations. ExAC catalogues exome data from 60,706 unrelated individuals sequenced from numerous disease-specific and population genetic studies. The ExAC website has been visited over 5.2 million times, and currently receives about 70,000 page views per week.

In a sub-analysis of the new Nature paper, the authors analysed 192 pathogenic variants reported in other studies, finding only nine with sufficient data supporting a conclusion that these variants had a strong disease association.

"Large-scale reference datasets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes," says Dr Lek.

"This analysis reveals global patterns of genetic variation providing resolution that hasn't been possible with smaller datasets of genetic variation."

Exome sequencing is a method for sequencing a subset of the human DNA genome that encodes proteins, known as exons. Humans have about 180,000 exons, constituting about one per cent of the human genome, or approximately 30 million base pairs. A base pair is a unit comprising two nucleotide bases bound to each other that form the building blocks of the DNA double helix. The human genome contains about 3.2 billion nucleotides and about 23,500 genes.

Three-quarters of the known genetic disease-causing variants are located in the protein-coding exome. Given the cost and technical challenges in analysing the all genomic sequence data, researchers are focusing much of their research primarily on exome sequencing.

Interpreting findings is a significant challenge at the heart of genetic sequencing. Each exome contains about 13,500 single nucleotide variants that change the amino acid and a large number of these are expected to be functional variants. The daunting task for medical researchers is to distinguish variants that are pathogenic from those that have little or no detectable clinical effects.
-end-


University of Sydney

Related Human Genome Articles:

Science and legal experts debate future uses and impact of human genome editing in Gender & the Genome
Precise, economical genome editing tools such as CRISPR have made it possible to make targeted changes in genes, which could be applied to human embryos to correct mutations, prevent disease, or alter traits.
Evolution purged many Neanderthal genes from human genome
Neanderthal genetic material is found in only small amounts in the genomes of modern humans because, after interbreeding, natural selection removed large numbers of weakly deleterious Neanderthal gene variants, according to a study by Ivan Juric and colleagues at the University of California, Davis, published Nov.
Mathematical analysis reveals architecture of the human genome
Mathematical analysis has led researchers in Japan to a formula that can describe the movement of DNA inside living human cells.
Navigating the human genome with Sequins
Australian genomics researchers have announced the development of Sequins -- synthetic 'mirror' DNA sequences that reflect the human genome.
Scientists cut 'Gordian knot' in the human genome
Females have two X chromosomes in each of their cells.
Guidelines for human genome editing
As countries around the world seek to craft policy frameworks governing the powerful new genetic editing tool, policy makers need to determine 'thresholds of acceptability' for using the technology, according to three researchers from the Centre of Genomics and Policy at McGill University.
Predicting the human genome using evolution
By observing evolution's 'greatest hits' (and misses) and the history of the major themes and patterns of genome conservation (and divergence) across many species, Temple University professor Sudhir Kumar's approach predicts probable mutations that will be found among people and the fate of human variation.
JAX reseachers, collaborators report on variations in human genome
A consortium of international researchers, including Charles Lee, Ph.D., of The Jackson Laboratory for Genomic Medicine, have reported findings from a massive research project exploring variations in the human genome, including structural variations.
Scientists discover new system for human genome editing
A team including the scientist who first harnessed the revolutionary CRISPR-Cas9 system for mammalian genome editing has now identified a different CRISPR system with the potential for even simpler and more precise genome engineering.
The human genome: A complex orchestra
A team of Swiss geneticists from the University of Geneva, the École Polytechnique Fédérale de Lausanne, and the University of Lausanne discovered that genetic variation has the potential to affect the state of the genome at many, seemingly separated, positions and thus modulate gene activity, much like a conductor directing the performers of a musical ensemble to play in harmony.

Related Human Genome Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#530 Why Aren't We Dead Yet?
We only notice our immune systems when they aren't working properly, or when they're under attack. How does our immune system understand what bits of us are us, and what bits are invading germs and viruses? How different are human immune systems from the immune systems of other creatures? And is the immune system so often the target of sketchy medical advice? Those questions and more, this week in our conversation with author Idan Ben-Barak about his book "Why Aren't We Dead Yet?: The Survivor’s Guide to the Immune System".