Public release date: 23-Mar-2009
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BioMed Central

Genomic variations in African-American and white populations
Deletions, duplications or rearrangements of genomic regions in the human genomes produce differences in gene copy numbers, referred to as copy number variations (CNV). Those variations account for a substantial portion of human genetic diversity, and in a few cases, have been associated with behavioural traits or increased susceptibility to disease. A study published today in the open access journal BMC Genetics, describes a CNV map of the African American genome, and compares frequencies of CNVs between African American and white American/European populations.

Joseph P McElroy and colleagues from the Department of Neurology, University of California at San Francisco, recruited African Americans from 28 States and used their genomes to draw CNV comparisons with the White dataset. "To the best of our knowledge, this is the first detailed map of copy number variations in African Americans. Understanding the distributions of CNVs in a population is a first step to addressing their role in disease".

The authors employed an array of over 500,000 sequences whose position in the human genome is already known due to single nucleotide polymorphisms. They first analysed the interaction of 50 blood samples of healthy African American females with this gene chip platform, and then used the results as a reference to assess copy number variation in samples from a further 385 African Americans, and an additional set of samples from 435 White individuals. In total, 1362 CNVs were detected in African Americans and 1972 in the White cohort. Across most of the genome, the frequency of CNVs did not differ greatly between the two populations. However, there were two duplications, one on chromosome 15, and one on chromosome 17, whose frequency varied markedly between the two groups.

The research team discovered that the duplication in chromosome 17 (region 17q21) is present in 45% of White but only in 8% of African American individuals. Another independent study has implicated the same region in mental retardation caused by a deletion due to duplication. Among the deleted genes, two of them, CRHR1 (corticitropin releasing hormone receptor 1) and MAPT (microtubule-associated protein tau), were previously associated with some neurological disorders. These two genes are not contained within the 17q21 region of CNV duplication, but map very close to it.

According to McElroy, "It would be good to know if the CNV duplication of the region might have an effect on the expression of these genes, which in turn could result in neurological disease. It is also interesting to find out whether the type of mental retardation associated with this locus is more common in Whites than in Africans or African Americans. If this is true, then it might be one of the first reported diseases with differing ethnic frequencies due to CNVs."


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Rosetta Biosoftware Announces the Syllego System Version 3.5 with Support for Copy Number Variation

March 16, 2009 08:00 AM Eastern Daylight Time
Rosetta Biosoftware Announces the Syllego System Version 3.5 with Support for Copy Number Variation
New Software Release Mitigates Data Challenges, Improves Research Productivity for Integrative Genomic Studies
Cambridge Healthtech Institute's Comprehending Copy Number Variation Conference
SEATTLE--(BUSINESS WIRE)--Rosetta Biosoftware, a global leader in life science informatics solutions, today announced the availability of copy number variation (CNV) data management and analysis capabilities in the latest release of the Syllego™ system. Syllego version 3.5 also offers scientists the ability to co-analyze gene expression (GE), CNV and genotyping data through enhanced statistical and visualization features and a data exchange gateway to the Rosetta Resolver® system. The new software release adds CNV to the Syllego system's current support for genome-wide association (GWA), linkage and eQTL studies, improving research productivity and expanding the software system's effectiveness in addressing the informatics challenges of scientists engaged in integrative genomic research.
In recent years, the existence of copy number as a common form of genetic variation, and its ability to influence phenotype, have been well established. Copy number variation is the subject of an increasing set of investigations to determine the extent and nature of its role in complex diseases. These studies look beyond single nucleotide polymorphisms (SNPs) in an effort to create a more complete picture of the associations between genetic variation and disease-related phenotypes. The need to manage, integrate and derive complicated dependencies between diverse data types – copy number, SNP, gene expression and phenotypic – from both public and proprietary sources is central to the success of this research. Syllego version 3.5 mitigates these challenges by providing
a common repository for commercial and custom copy number data and associated phenotypic data
a platform to integrate public copy number variation, genome data with proprietary data and analyze the composite data set
integrative analysis of genotyping, copy number variation and gene expression datasets
an open analysis platform that allows researchers to instantly use new public or proprietary analysis methods in easy-to-use interfaces
geneticists, biologists, informaticians and IT specialists with a single software solution to perform data management, data analysis, store results, and visualize results
"With the addition of CNV support, scientists can now use the Syllego system to interrogate complex data and find answers they've not been able to find before," said Yelena Shevelenko, General Manager, Rosetta Biosoftware. "We continue to execute on our strategy to deliver innovative technology to life scientists as they transform our understanding of biology and shape a new future for healthcare."
The Syllego system version 3.5 will be showcased at Cambridge Healthtech Institute's Comprehending Copy Number Variation Conference in San Diego on March 16, 2009; and during a Webinar hosted by Rosetta Biosoftware on March 25, 2009 at 9:00 AM Pacific Daylight Time. For more information, visit www.rosettabio.com/company/events.
About the Syllego System
The Syllego system is Rosetta Biosoftware’s practical solution for genetic data management and analysis. The Syllego system includes the Affymetrix GeneChip®-compatible designation and is part of the Illumina® Connect program. For more information on the Syllego system, please visit www.rosettabio.com/syllego.
About Rosetta Biosoftware
Rosetta Biosoftware is a leading provider of informatics solutions for life science research. Its comprehensive software solutions, including the Rosetta Resolver, Rosetta Elucidator, and Syllego systems, empower life scientists with advanced, scalable, and easy-to-use analysis platforms that accelerate discovery research. Rosetta Biosoftware is a business unit of Rosetta Inpharmatics LLC, a wholly-owned subsidiary of Merck & Co., Inc. More information about Rosetta Biosoftware is available at www.rosettabio.com.
Forward-Looking Statements
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential, or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Neither Rosetta Inpharmatics nor Merck & Co., Inc. undertakes any obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect the business of Merck & Co., Inc. including, among others, the extent to which Rosetta Inpharmatics' technology platform can be used in drug discovery programs, uncertainty of market acceptance of Rosetta Inpharmatics' technologies, ability to compete against existing technologies, and those mentioned in the cautionary statements in Item 1 of Merck’s Form 10-K for the year ended Dec. 31, 2008, and in its periodic reports on Form 10-Q and Form 8-K (if any) which are incorporated by reference.
Rosetta Resolver, Resolver, Elucidator, and Syllego are trademarks of Rosetta Inpharmatics LLC.

Are CNVs a Product of Paternal Age?

1: PLoS Med. 2009 Mar 10;6(3):e40. [Epub ahead of print] Links
Advanced Paternal Age Is Associated with Impaired Neurocognitive Outcomes during Infancy and Childhood.Saha S, Barnett AG, Foldi C, Burne TH, Eyles DW, Buka SL, McGrath JJ.
BACKGROUND: Advanced paternal age (APA) is associated with an increased risk of neurodevelopmental disorders such as autism and schizophrenia, as well as with dyslexia and reduced intelligence. The aim of this study was to examine the relationship between paternal age and performance on neurocognitive measures during infancy and childhood. METHODS AND FINDINGS: A sample of singleton children (n = 33,437) was drawn from the US Collaborative Perinatal Project. The outcome measures were assessed at 8 mo, 4 y, and 7 y (Bayley scales, Stanford Binet Intelligence Scale, Graham-Ernhart Block Sort Test, Wechsler Intelligence Scale for Children, Wide Range Achievement Test). The main analyses examined the relationship between neurocognitive measures and paternal or maternal age when adjusted for potential confounding factors. Advanced paternal age showed significant associations with poorer scores on all of the neurocognitive measures apart from the Bayley Motor score. The findings were broadly consistent in direction and effect size at all three ages. In contrast, advanced maternal age was generally associated with better scores on these same measures. CONCLUSIONS: The offspring of older fathers show subtle impairments on tests of neurocognitive ability during infancy and childhood. In light of secular trends related to delayed fatherhood, the clinical implications and the mechanisms underlying these findings warrant closer scrutiny.

PMID: 19278291 [PubMed - as supplied by publisher]

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Children Of Older Dads Do Less Well In Intelligence Tests

Pediatrics / Children's Health News

Children Of Older Dads Do Less Well In Intelligence Tests Featured ArticleMain Category: Pediatrics / Children's HealthAlso Included In: Fertility; Men's healthArticle Date: 11 Mar 2009 -
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0 postsResearchers from Australia looking at data on US families found that young children of older fathers performed less well in a range of cognitive intelligence tests up to the age of 7 years, but were unable to say whether those children were able to catch up when they got older.The study was the work of Sukanta Saha from the Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Richlands, Australia, and colleagues from other research centres in Australia, and was published online in the open access journal PLoS Medicine.There is good evidence that specific disorders are linked with older fathers, but the link between children's general intelligence and fathers' age is not very clear, said an editorial comment accompanying the article. One study has shown a link between lower intelligence and very young and older fathers, so the authors wanted to look at the issue more closely and see if there was a link between age of fathers and children's ability on intelligence tests. They also wanted to see if there was evidence to support another finding that older mothers tend to have more intelligent children.For the study the researchers looked at records from the US Collaborative Perinatal Project, and analyzed data on 33,437 children who had undergone tests of cognitive ability at 8 months, 4 years and 7 years. The tests measured children's ability to think and reason, assessing things like concentration, memory, learning, understanding, speaking, and reading. Some tests also assessed physical co-ordination or "motor skills".The tests included the Wechsler Intelligence Scale for Children, Bayley scales, the Stanford Binet Intelligence Scale, the Graham-Ernhart Block Sort Test, and the Wide Range Achievement Test.Saha and colleagues analyzed the data using two models. In the first model they took into account physical factors such as the age of the parents. In the second model they added social factors such as parents' education and income, both factors that are known to affect intelligence. The researchers also grouped the children according to maternal age, and within each group looked for links between the lowest scores and paternal age.They found that the older the father, the poorer the results (the exception was the Bayley Motor score), but there was no such link with the age of the mother; in fact maternal age was "was generally associated with better scores on these same measures", they wrote.Saha and colleagues also wrote that the "findings were broadly consistent in direction and effect size at all three ages". They concluded:"The offspring of older fathers show subtle impairments on tests of neurocognitive ability during infancy and childhood.""In light of secular trends related to delayed fatherhood, the clinical implications and the mechanisms underlying these findings warrant closer scrutiny," they added.The sudy is the first to show that older fatherhood gives rise to children that perform less well on intelligence tests when young, but it can't say whether these children catch up with their peers after the age of 7.The editorial comment also cautioned that the results could be biased because some of the records did not have any information on the father's age.The last few decades have seen an increasing trend in the developing world toward couples waiting until their late thirties to have children. And while we have known for some time that older mothers are more likely to give birth to children with disabilities like Down's syndrome, it wasn't until recently that we discovered older fatherhood might also bring risks.We now know that older fatherhood is linked to miscarriages, birth deformities, cancer, and brain development disorders such as autism and schizophrenia, as well as dyslexia and reduced intelligence.Rates of autism have gone up in recent decades, but nobody knows why; some suspect it is genetic, others that it could be damage to sperm, which increases as a man gets older. While women's eggs are formed in the female fetus before she is born and stay like that until they are fertilized and develop into a baby, a man's sperm keeps dividing throughout his life, increasing the chance of mutation.Some studies suggest that children of older mothers benefit because they are nurtured more at home. If that is the case, then it appears that children of older fathers don't experience this benefit.But this study cannot answer these questions, it can only point to the need for more research, and perhaps emphasize the importance of doing so, especially as the trend toward older fatherhood appears likely to continue."Advanced Paternal Age Is Associated with Impaired Neurocognitive Outcomes during Infancy and Childhood."Saha S, Barnett AG, Foldi C, Burne TH, Eyles DW, Buka SL and McGrath JJ.PLoS Medicine Vol. 6, No. 3, e40. Published online March 10, 2009.doi:10.1371/journal.pmed.1000040