Tallness And Height Gene Discoveries

From source Med Page Today and American Journal of Human Genetics

So I found this article and I felt that it was a nice addition to the site to show just how many genes and factors have been found so far that seems to influence the human height. It is really overwhelming and at this, point I don’t think geneticists and scientists can do gene therapy to increase height on a potential embryonic specimen.

My suggestion is similar to what the doctors are saying right now. We want to focus on learning about the possible ways height decreased disorders come about and learn their mechanism. If we can disrupt the genetic mechanistic pathway of the process, at least we can prevent and treat people who are suffering from pathologies leading to height deficiencies and prevent people from growing short.

Again, I will highlight the parts which I found the most important.


Tallness Gene Discoveries Could Give Legs to Other Research

By Crystal Phend, Senior Staff Writer, MedPage Today

Published: December 30, 2010

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

Action Points

  • Explain that scientists probing the genetics of height have discovered dozens more uncommon variants, adding to the nearly 200 already known.
  • Note that the study was a meta-analysis of studies done using the same genotyping chip with dense coverage of genes for uncommon single nucleotide polymorphisms (SNPs) and detected 30 new signals missed by regular chips in the past.
  • Explain that the researchers expect their process to be helpful in unraveling the genetics of complex diseases such as diabetes and MS.

Using a process that could help unravel the causes of a variety of complex diseases, scientists probing the genetics of height have discovered dozens more uncommon variants, adding to the nearly 200 already known.

Meta-analysis of studies using the same genotyping chip with dense coverage of genes for uncommon single nucleotide polymorphisms (SNPs) turned up 30 new signals missed by regular chips in the past, Hakon Hakonarson, MD, PhD, of Children’s Hospital of Philadelphia, and colleagues reported online in the American Journal of Human Genetics.

Still more variants remain to be found, Hakonarson’s group noted.

One recent analysis suggested that about 300,000 SNPs would be required to explain just 45% of the variance in height across the population, they wrote.

That’s a situation that may be similar to the genetics underlying some common health problems, Hakonarson explained in an interview.

“The ultimate goal is really to look at heart disease, cardiovascular risk factors, and diabetes,” he told MedPage Today.

Executive director or the American College of Medical Genetics, Michael S. Watson, PhD, agreed that the study carries broad implications for genetic research.

This study offers a reality check on how complex it can get with many, many genes involved plus environmental factors, and still only a minority of the heritability of the trait identified,” Watson wrote in an e-mail to MedPage Today and ABC News.

Few diseases are caused by so-called one-hit genetic mutations, noted Jerry W. Shay, PhD, of the University of Texas Southwestern Medical Center in Dallas.

“Most human diseases such as cancer, type 1 diabetes, multiple sclerosis, Crohn’s disease, and psychiatric disorders are much more complicated and may involve interplay between multiple genetic and epigenetic changes and the environment,” he said in an e-mail to MedPage Today and ABC News.

Understanding the genetic basis of something as straightforward as height is just the tip of the iceberg,” he added. “It is proof that our DNA contains valuable information that we are only beginning to dissect.”

Hakonarson’s group used height as a prototype to determine what could be done mining into known genes in greater detail with more density of the SNPs in each gene.

The researchers pooled results from 47 studies that genotyped 114,223 adults across six ethnicities using a gene chip targeted to cardiovascular-related gene loci but still contained many plausible height-related loci.

Comparing height to the results on the nearly 50,000 SNPs across about 2,000 loci, a total of 64 loci contained an SNP that predicted height with array-wide significance (P<2.4 x 10-6).

Among them, 42 loci exceeded the conventional genome-wide significance threshold of P<5 × 10-8.

Although 20 of the 64 had previously been described in studies as linked to height, Hakonarson’s group identified associations with several new regions containing genes with “interesting biological roles,” including growth hormone receptor, glucokinase regulatory protein, circadian rhythm, and collagen formation.

They paid special attention to variants of lower minor allele frequency (carried by less than 5% of the population) “that would go undetected in studies relying on imputation or in studies with fewer participants” and found 22 such SNPs in eight loci significantly associated with height.

Such genetic findings could be clinically useful in evaluating children of short stature of unknown cause, commented Ronald Bachman, MD, a geneticist at Kaiser Permanente in Oakland, Calif.

However, there’s limited value for the general public, and height shouldn’t be the subject of consideration for direct-to-consumer genetic testing, he warned.

“The interpretation of the results would probably lead to a great deal of stress and then perhaps unnecessary testing and treatments,” Bachman said in an e-mail to MedPage Today and ABC News.

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