A Brilliant Explanation of the Male Biological Clock

Male Biological Clock

CNVs vs SNPs: Understanding Human Structural Variation in Disease

Advancing paternal age causes copy number variations Science Webinar: CNVs vs SNPs July 12, 2008
Posted by Bertalan Meskó in Webinar, science.
trackback
Science Magazine will organize a webinar about copy number variations and single nucleotide polymorphisms.


CNVs vs SNPs: Understanding Human Structural Variation in Disease

July 16, 2008 at 12 noon Eastern Time (9 a.m. Pacific, 4 p.m. GMT)

Genetic variation—differences in both the coding and noncoding portions of our DNA—is what makes each human being a unique individual. It also can determine our unique susceptibility to disease. Exhaustive analysis of human single nucleotide polymorphisms (SNPs) has led to the identification of interesting SNP markers for certain disorders. But these small changes are not the whole picture. Copy number variations (CNVs)—gain or loss of segments of genomic DNA relative to a reference—have also been shown to be associated with several complex and common disorders. Using array-based comparative genomic hybridization (CGH) techniques, CNVs at multiple loci can be assessed simultaneously allowing for their identification and characterization. CNV microarrays allow exploration of the genome for sources of variability beyond SNPs that could explain the strong genetic component of several of these disorders. Now, advances in microarray probe density have provided more comprehensive coverage of CNVs, enabling more in depth genotyping research.

You can register here!

Speakers:

Charles Lee, Ph.D., FACMG; Department of Pathology, Brigham and Women’s Hospital, Boston MA
Lars Feuk, Ph.D., The Centre for Applied Genomics; The Hospital for Sick Children, Toronto, Ontario
Alexandra I Blakemore, Ph.D., Division of Medicine, Imperial College London, United Kingdom
The moderator will be Sean Sanders, Ph.D., Commercial Editor, Science/AAAS.

CCR5 haplotypes HHE and HHG*2 strongly influence the risk of SLE

--------------------------------------------------------------------------------

Published Online First: 30 October 2007. doi:10.1136/ard.2007.078048
Annals of the Rheumatic Diseases 2008;67:1076-1083
Copyright © 2008 BMJ Publishing Group Ltd & European League Against Rheumatism
--------------------------------------------------------------------------------



CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosus
M Mamtani 1, B Rovin 2, R Brey 3, J F Camargo 1, H Kulkarni 1, M Herrera 1, P Correa 4, S Holliday 5, J-M Anaya 4,6, S K Ahuja 1,7
1 The Veterans Administration Center for AIDS and HIV-1 Infection, South Texas Veterans Health Care System and Department of Medicine, University of Texas Health Science Center at San Antonio, Texas, USA
2 The Ohio State University College of Medicine and Public Health and Davis Heart and Lung Research Institute, Columbus, Ohio, USA
3 Department of Neurology, University of Texas Health Science Center at San Antonio, Texas, USA
4 Cellular Biology and Immunogenetics Unit, Corporacion para Investigaciones Biologicas, Medellin, Colombia
5 Psychology Service, South Texas Veterans Health Care System, San Antonio, Texas, USA
6 School of Medicine, Universidad del Rosario, Bogota, Colombia
7 Departments of Microbiology and Immunology, and Biochemistry, University of Texas Health Science Center, San Antonio, Texas, USA


Correspondence to:
S K Ahuja, Veterans Administration Center for AIDS and HIV infection, University of Texas Health Science Center, 7703 Floyd Curl Drive, Room 5.009R, San Antonio, Texas, 78229-7870, USA; ahujas@uthscsa.edu

Objectives: There is an enrichment of immune response genes that are subject to copy number variations (CNVs). However, there is limited understanding of their impact on susceptibility to human diseases. CC chemokine ligand 3 like-1 (CCL3L1) is a potent ligand for the HIV coreceptor, CC chemokine receptor 5 (CCR5), and we have demonstrated previously an association between CCL3L1-gene containing segmental duplications and polymorphisms in CCR5 and HIV/AIDS susceptibility. Here, we determined the association between these genetic variations and risk of developing systemic lupus erythaematosus (SLE), differential recruitment of CD3+ and CD68+ leukocytes to the kidney, clinical severity of SLE reflected by autoantibody titres and the risk of renal complications in SLE.

Methods: We genotyped 1084 subjects (469 cases of SLE and 615 matched controls with no autoimmune disease) from three geographically distinct cohorts for variations in CCL3L1 and CCR5.

Results: Deviation from the average copy number of CCL3L1 found in European populations increased the risk of SLE and modified the SLE-influencing effects of CCR5 haplotypes. The CCR5 human haplogroup (HH)E and CCR5-32-bearing HHG*2 haplotypes were associated with an increased risk of developing SLE. An individual’s CCL3L1–CCR5 genotype strongly predicted the overall risk of SLE, high autoantibody titres, and lupus nephritis as well as the differential recruitment of leukocytes in subjects with lupus nephritis. The CCR5 HHE/HHG*2 genotype was associated with the maximal risk of developing SLE.

Conclusion: CCR5 haplotypes HHE and HHG*2 strongly influence the risk of SLE. The copy number of CCL3L1 influences risk of SLE and modifies the SLE-influencing effects associated with CCR5 genotypes. These findings implicate a key role of the CCL3L1–CCR5 axis in the pathogenesis of SLE.

Additionally the risk of autism, epilepsy or schizophrenia also increased in these kids, which led to accidental deaths as well,

Man's Ability to Have Kids is Dependent on His Age



Written by Theresa Maher
Monday, 07 July 2008
MONDAY, July 7, (News Locale) - Contrary to popular perception, a man is not able to have kids anytime he wishes. New research out of France indicates male fertility is also dependent on age and men who delay fatherhood may have a tough time conceiving later on.
It is believed that unlike women, men have no biological clock and can father children throughout their life. In fact it is not uncommon to see celebrities having babies well after they have crossed their 50s.

Now researchers at the Eylau Centre for Assisted Reproduction in Paris have revealed men who delay fatherhood have a less chance of impregnating their partners.

The study of more than 20,000 couples who sought fertility help at the center found men over the age of 35 are almost a third less likely to conceive as compared to their younger counterparts. Furthermore men over the age of 40 had poor quality of sperm, which could lead to frequent miscarriages in their partners. In fact the risk of miscarriage if the father was over the age of 40 was 75 percent.

Researchers believe the DNA in sperm starts to decay with age and this may be the cause of fertility issues in older men.

The details of the study were presented at the European Society of Human Reproduction and Embryology conference.

An earlier study by Danish researchers had revealed kids born to older fathers were more likely to die before they entered adulthood when compared to kids born to younger fathers. This incidence was attributed to the declining quality of sperm due to ageing.

The scientists found that congenital defects like heart and spine problems were the main cause of death in these children.

Additionally the risk of autism, epilepsy or schizophrenia also increased in these kids, which led to accidental deaths as well, the researchers had reported in the European Journal of Epidemiology.

Consumers must be aware that the mother's age has always been associated with pregnancy complications. The above study provides evidence that a father's age may also have a say in conception.

'Miscarriage rate rises with age of father' CNVs?

'Miscarriage rate rises with age of father'

By Steve Connor, Science Editor
Monday, 7 July 2008


Women with older partners may be at higher risk of suffering miscarriages irrespective of their own age, according to a study that has linked the increased chance of a failed pregnancy with men over the age of 40.