<img loading="lazy" decoding="async" class="alignright size-full wp-image-3655" title="anopheles_gambiae" src="https://blog-api.23andme.com/wp-content/uploads/2009/05/anopheles_gambiae.png" alt="" width="350" height="196" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/05/anopheles_gambiae.png 350w, https://blogcms.23andme.com/wp-content/uploads/2009/05/anopheles_gambiae-300x168.png 300w" sizes="auto, (max-width: 350px) 100vw, 350px" />
Malaria is one of the leading causes of death in the developing world, claiming nearly a million victims each year. The great majority of them are African children below the age of five. The illness is caused by a single-celled parasite called Plasmodium that is transmitted by mosquito bites to humans. In a paper published today in <a href="https://www.nature.com/ng/journal/vaop/ncurrent/abs/ng.388.html" target="_blank" rel="noopener noreferrer">Nature Genetics</a>, a group of African and British doctors and scientists report on their study of the genetic roots of malaria susceptibility. They found no new smoking gun with this effort, but learned much about how to improve African genetic studies in the future.

The researchers gathered the SNP genotypes of 2,500 children, with the consent of their parents, from a small region in The Gambia. About 1,000 of the children had been admitted to the hospital with a case of severe malaria – the other 1,500 were newborns. In a <a href="https://www.genome.gov/20019523" target="_blank" rel="noopener noreferrer">genomewide association study</a>, the researchers checked each of a half-million SNPs (single nucleotide polymorphisms) for sharp differences in genetic composition between the group of children suffering from malaria and the group of newborns, who served as an approximation of a malaria-free group. If one version of an individual SNP was seen at high frequency among the malaria victims, but at low frequency in the newborns, then the difference might be because the SNP tends to cause malaria or is nearby one that does.
Upon scanning their data, the researchers came up more or less empty-handed: by the usual standards of the field, none of the 500,000 SNPs would pass muster.
This deflating result stands at odds with what is known already about the genetics of malaria susceptibility. Most people who have taken a biology class learn that human populations in malarial regions have developed a natural immunity to malaria infection, not through their immune systems, but through a genetic modification of hemoglobin. Hemoglobin is a molecule charged with ferrying oxygen from your lungs (and the lungs of most life forms that have them) to all your cells, an essential task. Biologists have traced hemoglobin-based malaria resistance to a change at a single DNA base pair on chromosome 11 – wouldn&#8217;t we expect at least this SNP to light up as significant?
In truth, the failure wasn&#8217;t so surprising; it arises from the interplay of genetics with our species&#8217; history. Humans first arose in Africa, so that&#8217;s where genetic variation has had the longest time to build up. Modern-day Asian, European, and Native American people descend from people who emigrated from Africa about 50,000 years ago. These migrants carried just a subset of the African gene pool with them, so non-African populations today have much less &#8220;well-mixed&#8221; genomes than African populations. The present study uses genotyping chips developed for use in European populations, and its failure to find the known hemoglobin SNP (which isn&#8217;t even genotyped by the chip) and other known genetic contributors to malaria resistance is essentially due to the fact that you&#8217;d need more like two million SNPs than half a million to do the job right.
The solution, you&#8217;d think, is just to make a chip with a lot of markers for specific use in Africa, and be done with it. But the authors show that African genomes appear to be mixed so well that no single such chip could be designed. Instead, they propose an alternative approach: use a good but inevitably suboptimal African SNP chip in your full study sample, then obtain full genome sequences from a small number of the members of that sample. Then, using a powerful statistical method called imputation, you use the full sequences of the smaller group to fill in the full genomes of the entire study sample based on their SNP genotypes. This approach, as the authors demonstrate convincingly in the case of hemoglobin-based malaria resistance, would provide a statistically powerful and economically viable means of tracking down the causes of some of the most challenging health problems of our time.

23andMe Blog

23andMe Blog Team

Gloom but not Doom, Concludes Study in Malaria Area

<img loading="lazy" decoding="async" class="alignright wp-image-3644 size-full" title="pastrana1" src="http://35.88.189.111/wp-content/uploads/2009/05/pastrana1.jpg" alt="" width="300" height="576" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/05/pastrana1.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2009/05/pastrana1-156x300.jpg 156w" sizes="auto, (max-width: 300px) 100vw, 300px" />
Congenital general hypertrichosis (CGH) is one of humans&#8217; most unusual genetic conditions. Sometimes known as &#8220;bearded lady syndrome,&#8221; it leads to excessive hair across the body and faces at levels much higher than the normal range for humans.   The condition has been of interest for centuries, becoming more well-known during the 19th century as P.T. Barnum&#8217;s traveling circuses began exhibiting those suffering from it.   Most famously,   <a href="https://en.wikipedia.org/wiki/Julia_Pastrana" target="_blank" rel="noopener">Julia Pastrana</a> (pictured, right), a Mexican-born woman afflicted with CGH, was exhibited in circuses across the United States and Europe during the mid-19th century.   She was often described as not only being excessively hairy all over her body and face, but of having a wide nose, enlarged gums, and overall &#8216;ape-like&#8217; features.
Since the Middle Ages, when this condition was first reported, there has been much speculation over the root causes of CGH. Some have argued that CGH is an example of atavism or an evolutionary &#8216;throwback&#8217; to a more primitive ancestor.   Others have reasoned (incorrectly) that individuals suffering from CGH represented the missing link between apes and humans, and thus, further evidence to support Darwin&#8217;s theory of evolution.
Because CGH tends to run in families, many believed there was a genetic component to the condition.   A team of geneticists led by Xue Zhang of the Chinese Academy of Medical Scientists have uncovered the genetic basis for this condition after examining several families with a history of CGH.   Their results are described in the June 12 issue of the <a href="http://www.cell.com/AJHG/abstract/S0002-9297(09)00160-8" target="_blank" rel="noopener">American Journal of Human Genetics</a>.

One of the researchers&#8217; major challenges was simply finding subjects to study; there have been only a handful of confirmed cases over the past few hundred years.   Zhang and his team, however, were able to isolate several examples of CGH for study.   They examined three Han Chinese families whose members exhibited various degrees of a form of CGH known as congenital general hypertrichosis terminalis (CGHT).   This type of CGH usually causes overgrowth of very thick, dark hair on the face and body, enlarged gums and otherwise distorted facial features.   It is believed that Julia Pastrana suffered from CGHT.
The researchers also examined an unrelated Chinese individual with a severe case of the condition.   For the three Chinese families, the authors created a detailed pedigree in order to determine how CGH was passed down from generation to generation.   Then, they performed a high-resolution genetic analysis of each individual.   They found at least four distinct genes that were likely related to this condition, all on Chromosome 17.   The authors believe that mutations in these genes, specifically either insertions or deletions of strands of DNA within them, may be at the root of the condition.   In fact, there have been reports of CGH (or at least CGH-related symptoms) among individuals suffering from trisomy 17; when someone inherits three copies of chromosome 17 from his or her parents, rather than the standard two copies.
However, there are several different levels of severity of CGHT, as well as other types of CGH, so it is also clear that much more work must be done to tease out the precise molecular mechanisms for why these four genes on a particular stretch of chromosome 17 should be so central to the prevalence of this rare condition.

Genetics Behind “Bearded Lady Syndrome”

<img loading="lazy" decoding="async" class="alignright size-full wp-image-2970" title="autismawareness" src="https://blog-api.23andme.com/wp-content/uploads/2009/03/autismawareness.jpg" alt="" width="141" height="247" />
Researchers have identified <a href="https://blog.23andme.com/articles/snpwatch-connections-between-brain-cells-may-be-key-to-autism-puzzle/" target="_blank" rel="noopener">yet another</a> common genetic variation that appears to be associated with autism.   The results, published this week in the journal <a href="https://dx.doi.org/10.1038/mp.2009.41" target="_blank" rel="noopener">Molecular Psychiatry</a>, show that each copy of an G at in the CACNA1G gene increase the odds of autism in boys (but not girls) by about 2.2 times.
But Stanley Nelson, senior author of the study and a 23adMe scientific advisor, points out that the G version of this SNP is actually fairly common.
&#8220;Most people with the risk genotype will not develop autism.&#8221;
For more on this story:
<ul>
<li><a href="https://www.bloomberg.com/apps/news?pid=20601124&amp;sid=aLhQfJuxV8.s&amp;refer=home" target="_blank" rel="noopener">Gene May Offer Clue Why Autism Risk Is Fourfold Higher in Boys</a></li>
<li>A Genetic Clue to Why Autism Affects Boys More</li>
<li><a href="http://newsroom.ucla.edu/portal/ucla/ucla-scientists-identify-new-gene-92513.aspx" target="_blank" rel="noopener">UCLA scientists identify new gene linked to autism risk</a></li>
</ul>

Genetic Variation Linked to Autism Risk In Boys

<img loading="lazy" decoding="async" class="alignright size-full wp-image-3624" title="liver" src="https://blog-api.23andme.com/wp-content/uploads/2009/05/liver.jpg" alt="" width="350" height="260" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/05/liver.jpg 350w, https://blogcms.23andme.com/wp-content/uploads/2009/05/liver-300x223.jpg 300w" sizes="auto, (max-width: 350px) 100vw, 350px" />
A new report, published online today in the <a href="http://content.nejm.org/cgi/content/full/NEJMoa0810440" target="_blank" rel="noopener">New England Journal of Medicine</a>, shows that several variations in genes related to the immune system are associated with primary biliary cirrhosis (PBC), adding support to the theory that the condition is caused by an autoimmune reaction in which the body&#8217;s own defense system turns against itself.
PBC is a chronic disease that slowly destroys bile ducts within the liver. &nbsp; Inflammation causes bile to remain in the liver, leading to gradual injury and eventual scarring. People with PBC may remain symptom-free for many years after diagnosis, but cirrhosis can eventually lead to life-threatening complications. &nbsp; Women account for about 90 percent of PBC cases &#8212; up to one in 1,000 over 40 are affected by the condition. &nbsp; Studies have shown that genes influence the risk of developing PBC, but so far only a few genetic variations have been linked to the disease.
Gideon Hirschfield and colleagues analyzed the DNA from a total of 1,031 people with PBC and 2,713 controls, all with European ancestry. &nbsp; They found associations between several variations in the HLA region of the genome and the condition. &nbsp; The genes in this region of DNA encode proteins that help the body distinguish between its own tissues and foreign invaders like viruses and bacteria.
The researchers also identified variations in the IL12A and IL12RB2 genes, which encode proteins involved in immune system signaling.
Several other variations, many also in immune system-related genes, were also associated with PBC, though not as strongly as those detailed above.
According to the authors of the study, their findings will not only help scientists better understand the causes of PBC, but may also aid in the search for treatments. &nbsp; For instance, the authors suggest drugs that modify signaling by interleukin-12Î± and its receptor (encoded by the IL12A and IL12RB2 genes, respectively) might be beneficial for patients with PBC.

Researchers Link Variations In Immune System Genes with Primary Biliary Cirrhosis

<img loading="lazy" decoding="async" class="alignright size-full wp-image-3613" title="Grandparent and daughter" src="https://blog-api.23andme.com/wp-content/uploads/2009/05/istock_000004109962xsmall.jpg" alt="" width="331" height="270" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/05/istock_000004109962xsmall.jpg 383w, https://blogcms.23andme.com/wp-content/uploads/2009/05/istock_000004109962xsmall-300x245.jpg 300w" sizes="auto, (max-width: 331px) 100vw, 331px" />
No matter when it happens, puberty is no fun. &nbsp; But for girls, entering womanhood earlier or later than average can mean more than just the social awkwardness of being quick to mature or a late bloomer. &nbsp; It can have important health consequences later in life.
In general, girls in the developed world are maturing faster now than ever before. &nbsp; In the mid-nineteenth century the age at menarche (the first menstrual period, a milestone usually reached about two to three years after puberty begins) was about 16, but by the end of the twentieth century that number had fallen to about 13. Earlier age at menarche has been associated with an increased risk for breast, ovarian and endometrial cancer. On the other hand, later menarche is linked to increased risk for osteoporosis and cardiovascular disease.
Much of the change in the rate of maturation for girls has been attributed to better nutrition and rising rates of obesity, but new research shows that the age at menarche is also influenced by genetics.
Four papers (<a href="https://dx.doi.org/10.1038/ng.382" target="_blank" rel="noopener">Ong et al.</a>, <a href="https://dx.doi.org/10.1038/ng.383" target="_blank" rel="noopener">Sulem et al.</a>, <a href="https://dx.doi.org/10.1038/ng.386" target="_blank" rel="noopener">Perry et al.</a>, and <a href="https://dx.doi.org/10.1038/ng.385" target="_blank" rel="noopener">He et al.</a>), published online yesterday in the journal Nature Genetics, analyzed data from a total of more than 60,000 women with European ancestry and identified two regions of the genome that contain variations associated with small differences in age at menarche. &nbsp; One of these four studies, and a fifth paper (<a href="https://dx.doi.org/10.1038/ng.387" target="_blank" rel="noopener">Stolk et al.</a>), also found variations associated with the timing of menopause, the other end of the reproductive spectrum for women.
All four studies looking at age of menarche found a connection with a region of chromosome 6. Each paper identified slightly different variants, but they all appear to be zeroing in on a single, yet to be found, causative variation in the DNA. &nbsp; As an example of the effect of the chromosome 6 SNPs, Ong et al. found that compared to those with two Cs, each T at meant that woman got her first period about six weeks earlier.
Each T at was also associated with 1.20 times greater odds of breast development at age 10, 1.26 times greater odds of advanced breast development between the ages of 9 and 16 and a faster rate of increase in height and weight.
Although girls who go through puberty earlier than their peers are tall for their age during childhood, their growth stops sooner and they are generally shorter as adults. &nbsp; Ong et al. found that each T at was associated with a reduction in adult height of about 0.15 inches.
Two studies also found an association between variations on chromosome 9 with age at menarche. &nbsp; Each C at (the most significant SNP found in He et al.), for example, translated into about five weeks earlier menarche.
He et al. and Stolk et al. found variations in five regions of the genome associated with another big change in a woman&#8217;s life: menopause. The risks associated with the timing of menopause are the reverse of those associated with menarche: later menopause has been associated with higher risk for certain cancers and earlier menopause is linked to increased risk for osteoporosis and cardiovascular disease.
Finally, all of you boys and men out there need not feel left out: &nbsp; Ong et al. also looked at the effects of on puberty in males. &nbsp; They found that each copy of an T translated into 1.26 greater odds of advanced voice breaking at age 15, 1.19 times greater odds of advanced pubic hair at age 13, faster rate of growth at age 10 and about a tenth of an inch less in adult height.

Researchers Link Common Genetic Variations To Those Changes A Woman’s Body Goes Through

<img loading="lazy" decoding="async" class="alignright size-full wp-image-3598" title="Pregnant women holding a cigarette" src="https://blog-api.23andme.com/wp-content/uploads/2009/05/istock_000001159501xsmall.jpg" alt="" width="284" height="423" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/05/istock_000001159501xsmall.jpg 284w, https://blogcms.23andme.com/wp-content/uploads/2009/05/istock_000001159501xsmall-201x300.jpg 201w" sizes="auto, (max-width: 284px) 100vw, 284px" />
For many women, finding out they&#8217;re pregnant is the kick in the pants they need to quit smoking.   But for some, a genetic variation may stand in their way.
The SNP is located in a cluster of genes on chromosome 15 that are involved in regulating the brain&#8217;s response to nicotine. Studies have already shown that the SNP is associated with nicotine addiction. Now a new report, published online last week in the journal <a href="https://dx.doi.org/10.1093/hmg/ddp216 " target="_blank" rel="noopener">Human Molecular Genetics</a>, suggests that the effect of this variation is strong enough to overcome the maternal instinct and social pressure to protect one&#8217;s unborn child from the harmful effects of cigarette smoke.
British researchers studied 2,474 women who smoked regularly before becoming pregnant.   When questioned about smoking during their first trimester, <a href="http://www.eurekalert.org/pub_releases/2009-05/tpco-gae051309.php" target="_blank" rel="noopener">31% of the women</a> with two Gs at had kicked the habit, compared to only 21% of the women with two As.   During the third trimester, 47% of women with two Gs were smoke-free, while only 34% of women with two As were.
Overall, after adjusting for pre-pregnancy smoking quantity, the researchers calculated that each A at increases a woman&#8217;s odds of continuing to smoke throughout her pregnancy by about 1.2 times.
The authors say their results show how genes can influence what is perceived by many to be a matter of self-control but that &#8220;it&#8217;s in my genes&#8221; shouldn&#8217;t used as an excuse to avoid giving up smoking during pregnancy.

Genetic Variation May Make It Harder For Expectant Moms To Quit Smoking

Mexican flu virus genetics has been much in news lately; how about a look at Mexican human genetics for a  change?
A <a title="Goes to Silva-Zolezzi et al (2009)." href="https://www.pnas.org/content/early/2009/05/11/0903045106.abstract" target="_blank" rel="noopener noreferrer">new article</a> from researchers at Mexico&#8217;s National Institute for  Genomic Medicine (INMEGEN) examines genetic diversity across the nation and argues that, in order to conduct studies of common genetic diseases efficiently, a Mexico-specific genetic reference database should be built.
<div id="attachment_3569" style="width: 510px" class="wp-caption alignnone"><img loading="lazy" decoding="async" aria-describedby="caption-attachment-3569" class="size-full wp-image-3569" title="figure1_silva-zolezzi_etal_pnas_2009" src="https://blog-api.23andme.com/wp-content/uploads/2009/05/figure1_silva-zolezzi_etal_pnas_2009.png" alt="Map of Mexico with sampled states highlighted." width="500" height="390" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/05/figure1_silva-zolezzi_etal_pnas_2009.png 550w, https://blogcms.23andme.com/wp-content/uploads/2009/05/figure1_silva-zolezzi_etal_pnas_2009-300x235.png 300w" sizes="auto, (max-width: 500px) 100vw, 500px" />Map of Mexico with sampled-from states highlighted.</div>

Recent studies of genetic diversity among Europeans (blogged about <a title="Chris Gignoux on Tian et al (2009) in the Blog." href="https://blog.23andme.com/2008/08/13/a-different-kind-of-gene-mapping-comparing-genetic-and-geographic-structure-in-europe/" target="_blank" rel="noopener noreferrer">here</a> ) show that DNA is a surprisingly good predictor of where a person lives; people from the same country tend to be more similar to one another than to those from other parts of the continent. This latest study, which was published earlier this week in the <a href="https://www.pnas.org/">Proceedings of the National Academy of Sciences</a>, shows a similar pattern in Mexico: Mexican Mestizos (people of mixed European and Native American ancestry) from the same state tend to group together genetically, and the groups themselves fall along a genetic continuum that corresponds roughly to their latitude. You can see for yourself in this plot from the paper (below), which we’ve modified a bit for clarity. This is the same kind of plot used in 23andMe’s Global Similarity: Advanced feature  – each point in the plot represents a person. The closer two points appear in the plot, the closer those two individuals are to each other genetically. The 300 Mexican Mestizos fall into a line stretching from a group of Europeans at the upper right to a group of Amerindians1 at the lower left.
<div id="attachment_3568" style="width: 481px" class="wp-caption alignnone"><img loading="lazy" decoding="async" aria-describedby="caption-attachment-3568" class="size-full wp-image-3568" title="figure2b_silva-zolezzi_etal_pnas_2009-annotated" src="https://blog-api.23andme.com/wp-content/uploads/2009/05/figure2b_silva-zolezzi_etal_pnas_2009-annotated.png" alt="PCA map of Mexican genotypes." width="471" height="329" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/05/figure2b_silva-zolezzi_etal_pnas_2009-annotated.png 471w, https://blogcms.23andme.com/wp-content/uploads/2009/05/figure2b_silva-zolezzi_etal_pnas_2009-annotated-300x210.png 300w" sizes="auto, (max-width: 471px) 100vw, 471px" />PCA map of Mexican genotypes.</div>
<div>
The people from Sonora, the northernmost state, appear closest to the European cluster, and the people from the southern states Guerrero, Veracruz, and Yucatan appear closest to the Amerind cluster. This makes you wonder whether this pattern might correlate with the proportion of European ancestry. The researchers wondered that too, so they investigated further by analyzing their dataset with a computer program that estimates the proportion of ancestry a person&#8217;s DNA derives from each of several reference populations. When they set the program loose, they found that the six states did vary widely in proportion of European ancestry, from an average of 65% in Sonora (fifth column from the left) to an average of 35% in Guerrero (second from the right):
<div id="attachment_3572" style="width: 506px" class="wp-caption alignnone"><img loading="lazy" decoding="async" aria-describedby="caption-attachment-3572" class="size-full wp-image-3572" title="figure3b_silva-zolezzi_etal_pnas_2009-annotated" src="https://blog-api.23andme.com/wp-content/uploads/2009/05/figure3b_silva-zolezzi_etal_pnas_2009-annotated.png" alt="Admixture proportion estimates for Mexican and HapMap samples." width="496" height="247" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/05/figure3b_silva-zolezzi_etal_pnas_2009-annotated.png 496w, https://blogcms.23andme.com/wp-content/uploads/2009/05/figure3b_silva-zolezzi_etal_pnas_2009-annotated-300x149.png 300w" sizes="auto, (max-width: 496px) 100vw, 496px" />Admixture proportion estimates for Mexican and HapMap samples.</div>
</div>
The authors note that this pattern makes sense since Amerindian population density declines as you head north. Also, you might note that there&#8217;s a green sliver of African ancestry in each of the Mestizo populations, which approaches 5% in the southern states of Veracruz and Guerrero. This also meshes well with the historical record, since it&#8217;s through these coastal states, among others, that African slaves entered Mexico during the Spanish colonization.
These analyses tell us much about Mexico&#8217;s history  – could the same dataset serve to improve Mexico&#8217;s future? This paper also examines the prospects for conducting medical genetic studies in Mexico.
The most popular study design nowadays, and the one that the researchers focus on, is the genome-wide association study, or GWAS, also called a case-control study. GWASes are the basis for essentially all the studies discussed in the Blog, and the majority of the findings underlying 23andMe&#8217;s Health and Traits reports, and have recently been the subject of intense <a title="Erin Cline's Blog post on the NEJM GWAS dustup." href="https://blog.23andme.com/articles/328-genomewide-association-studies-and-counting-%E2%80%A6-what-now" target="_blank" rel="noopener noreferrer">debate</a> in the genetics community.
The core idea of a GWAS is to look for genetic markers (these days, usually common single-letter DNA variations known as SNPs) in a population that are at very different frequencies in a group of people with a particular disease, say type 2 diabetes, then in a group of people without that disease. In order to do that, you first have to identify a comprehensive set of the common genetic variations within a population, and then create a DNA array (commonly called a SNP chip) to probe all those variable locations in a large number of people with and without the condition you&#8217;re studying.
There&#8217;s the rub. In recent years, a project known as HapMap has created catalogs of common variations in European, African and East Asian populations, and chips have been produced based on it2. But Mexico&#8217;s population is a mixture of two of those (European and African) and another population (Amerindian) that are related, but not identical to, the third. There is no Mexican SNP chip.
That&#8217;s why the authors of this paper are suggesting a project to characterize common genetic variation within the Mexican population itself. They estimated that a catalog of common genetic variation using any two of the Mestizo groups they analyzed would capture enough variation to fuel quality GWAS studies, and would require fewer markers to do so than the alternative, which would be to use all the common markers from HapMap itself. This would substantially lower the cost of genotyping, they argue, and the reduced cost of using a platform based on the Mexico-specific catalog would allow researchers to genotype many more people for their GWAS studies for the same number of pesos. Since the sample size is often the limiting factor in the ability of the GWAS design to find disease genes, this could improve their ability to find the genetic causes of inherited disease.
Thanks to 23andMe Founding R&amp;D Architect Brian Naughton for his assistance in the preparation of this blog post.
Notes
<ol>
<li>Amerindian, sometimes just Amerind, is short for &#8220;American Indian&#8221;, and it denotes a descendant of the indigenous peoples of the Americas; anthropologist-types use the word to avoid confusion with the Indians that live in South Asia.</li>
<li>Because full-genome sequencing is still a few years from being affordable, researchers cannot look at every single one of the 3 billion nucleotides in the genome to find the one (or combinations of more than one) that are directly linked to a particular condition. For now, they must make do with the half-million to million SNPs that the current crop of SNP-genotyping chips allow. At first blush, this sounds like a fool&#8217;s errand. How can you possibly say anything about 3 billion DNA nucleotides with a collection of just a million markers? What if the marker you have on your SNP chip is near to but not actually the disease-causing SNP? Won&#8217;t this be like ships passing in the night? In just the last decade or so, geneticists have <a href="http://www.sciencemag.org/cgi/content/abstract/sci;310/5746/321?maxtoshow=&amp;HITS=10&amp;hits=10&amp;RESULTFORMAT=&amp;author1=Myers&amp;andorexacttitle=or&amp;andorexacttitleabs=or&amp;andorexactfulltext=or&amp;searchid=1&amp;FIRSTINDEX=0&amp;sortspec=relevance&amp;fdate=1/1/2005&amp;tdate=12/31/2005&amp;resourcetype=HWCIT,HWELTR">learned</a> that the human genome has a very peculiar property: the 22 numbered chromosomes, or autosomes, and the X, tend to do the bulk of their recombining in a very small fraction of the spans of those chromosomes. These highly-recombining locations are termed hotspots; it&#8217;s kind of like chromosomes are trains, with hotspots as the links between boxcars (although unlike boxcars, which are all the same length, there&#8217;s considerable variation in the distance between hotspots). This state of affairs is good news for GWASes, because it means that these boxcars – big chunks (mean length ~200,000 DNA base pairs) of chromosome that tend to be passed from parent to child as a unit – aid the task of marker selection greatly. If you sample a bunch of people, as these researchers have done in Mexico, then you can build up a catalog of the specific chromosome chunks that occur. The idea is that when a disease-causing allele occurs, it can&#8217;t help but sit on one of these chunks, so the problem of building a GWAS chip is transformed into choosing markers that reliably distinguish between the chunks. It&#8217;s like being able to assign one inspector to each boxcar, rather than each crate inside it. All you need to do, then, is to look at SNP that&#8217;s diagnostic for the chromosome chunk that your disease-causing SNP is sitting on, instead of having to find the causal SNP itself. The technical word for these chunks or boxcars is haplotype3, and such catalogs when built are called haplotype maps; it&#8217;s actually what was meant by the &#8220;medical genetic reference database&#8221; in the title of this post. It&#8217;s for the same purpose that the International HapMap Project, which has built reference haplotype maps for African, Asian, and European populations, was conceived, and it&#8217;s the origin of the name HapMap.</li>
<li>A haplotype is short for haploid genotype. Haploid means that you&#8217;re concerned with one chromosome, so haplotype means a contiguous segment from a single chromosome. Diploid means two (paired) chromosomes; humans are a diploid organism because our chromosomes come in pairs. The fun doesn&#8217;t stop there. Some organisms are tolerant of higher ploidy, so there are tetraploid, hexaploid, and even octoploid species. For example wheat is hexaploid, so it has six copies of each chromosome.</li>
</ol>

New Study Argues For Construction of Mexican Medical Genetic Reference Database

<img loading="lazy" decoding="async" class="alignright size-full wp-image-3542" title="kidneys" src="https://blog-api.23andme.com/wp-content/uploads/2009/05/kidneys.jpg" alt="" width="310" height="230" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/05/kidneys.jpg 350w, https://blogcms.23andme.com/wp-content/uploads/2009/05/kidneys-300x223.jpg 300w" sizes="auto, (max-width: 310px) 100vw, 310px" />
Chronic kidney disease (CKD), characterized by the gradual loss of the kidneys&#8217; filtering ability, currently affects about 10-13% of adults in the United States.   Patients suffering from the most severe form of the condition, end-stage renal disease, require dialysis or a kidney transplant to survive.
High blood pressure and diabetes are known risk factors for CKD, but evidence from multiple studies indicates that there is a genetic component to the condition too.   Rare mutations that cause <a href="https://www.23andme.com/topics/carrier/polycystic-kidney-disease/">kidney disease</a> have been identified, but finding common variations that impact susceptibility to CKD has been difficult.   Now a new study, published online this week in the journal <a href="https://dx.doi.org/10.1038/ng.377" target="_blank" rel="noopener noreferrer">Nature Genetics</a>, shows that a variation in the gene that encodes the most common protein found in urine is associated with kidney disease risk.

The Tamm-Horsfall protein, encoded by the UMOD gene, was discovered almost 60 years ago, but its role in the body continues to baffle scientists.   Some studies have suggested it may be involved in protection against inflammation and infection, while others have suggested it functions in kidney development.
&#8220;We have known for a long time that a higher level of proteins, such as albumin, which aren&#8217;t usually present in urine, is a risk factor for kidney disease and its progression. The UMOD finding suggests that Tamm-Horsfall protein, which is thought to be a normal part of the urine, deserves attention since its genetic variation relates to risk,&#8221; said Josef Coresh, professor in the Johns Hopkins Bloomberg School of Public Health&#8217;s Department of Epidemiology and Biostatistics and a co-author of the study, in a statement.
Another study from Johns Hopkins, appearing last year in <a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&amp;pubmedid=18794854" target="_blank" rel="noopener noreferrer">Nature Genetics</a>, found an association between variations in the MYH9 gene and end-stage renal disease in African Americans.

Variation In Urine Protein Gene May Decrease Risk Of Chronic Kidney Disease

Chronically high blood pressure is a serious health problem that affects about one out of every three adults and contributes to approximately 17.5 million deaths worldwide each year.   While there are many things people can do to try to keep their blood pressure down — lower salt intake, maintain a healthy weight, and drink in moderation — studies have shown that genetics also plays a part.
<h2>Genetic Influences</h2>
However, finding common genetic variations affecting blood pressure is difficult. Just five months ago The Blog reported on the first validated association in Europeans. Now, two large consortia have identified several more.   Their findings, published online this week in the journal Nature Genetics, expand the current understanding of how blood pressure is determined and may point the way toward targets for new drugs for treating and possibly preventing hypertension.
&#8220;None of the genes we identified as having common variation are part of the system we know about that regulates blood pressure — the genes identified are not the ones targeted by current prescription drugs to control hypertension.   If we can increase the number of genes implicated in blood pressure maintenance…our understanding of the biology will change completely,&#8221; said Aravinda Chakravarti, head of the Center for Complex Disease Genomics in the McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins University School of Medicine and a co-author of one of the studies, in a statement.
<h2>New Findings</h2>
The two research groups analyzed data from an enormous number of people — more than 50,000 in the <a href="https://dx.doi.org/10.1038/ng.361" target="_blank" rel="noopener noreferrer">Global BPgen</a> study and more than 29,000 in the <a href="https://dx.doi.org/10.1038/ng.384" target="_blank" rel="noopener noreferrer">CHARGE</a> study.   Such large samples are needed because variation in blood pressure is likely due to many variations, each with very small effects.
After conducting their own analyses, the researchers from each consortium shared their findings with each other, allowing the scientists to further confirm their results.   Altogether, six distinct variations associated with systolic blood pressure (SBP) and nine associated with diastolic blood pressure (DBP) were found and confirmed between the two studies. The Global BPgen consortium also studied more than 12,000 South Asian Indians and found evidence for an association between blood pressure and two of the SNPs identified in the European studies.
Further analysis of the Global BPgen results showed that all of the SNPs associated with SBP through the genomewide analysis were similarly related to DBP, and vice versa. And not surprisingly, all of the SNPs the researchers identified were also associated with hypertension; the version of each SNP linked to lower blood pressure was also decreased a person&#8217;s odds of having the condition.
The effects of the individual SNPs were small, but the authors of both studies point out that small changes in blood pressure can translate to important changes in the risk of heart disease and stroke.   For example, the authors of Global BPgen study say that lowering SBP by 2 mmHg has been estimated to translate into 6% lower risk of stroke and 5% lower risk of coronary heart disease.   The authors of the CHARGE study cite other data showing that a prolonged increase in DBP of 5 mm Hg is associated with a 34% increase in risk for stroke and a 21% increase in the risk of coronary events.

Latest Posts — Page 191