Researchers have identified several genetic variations associated with the timing of a baby’s first tooth and the number of teeth at age one. The results, published recently in the journal PLoS Genetics, could be important for understanding more about human health than just this rite of passage all babies must go through.

Nascent teeth form in the womb, but for most babies the first one doesn’t poke through the gums until sometime between four and seven months of age. Some little ones, however, begin teething as early as three months, while others may take a year or more to sprout their first pearly whites. Although the genetic bases for many syndromes involving serious problems with tooth formation have been discovered, until now not much work has been done to understand how our DNA impacts the normal variation in teething seen in the population.

British and Finnish researchers analyzed the DNA of about 6,000 people (approximately 1,500 from the U.K. and 4,500 from Finland) who had been followed by epidemiologists since early in their mothers’ pregnancies. Genetic variants in 10 different regions of the genome had at least a suggestive link to age at first tooth eruption and/or number of teeth at one year. Those SNPs with statistically significant associations with at least one of the traits are shown in the table below.

*= association not significant for tooth eruption; **= association not significant for number of teeth at age one.

Subjects are classified by the number of delayed tooth eruption alleles. SNPs are chosen so that they had the strongest signal for number of teeth at each locus. Mean time of first tooth eruption is plotted in red and number of teeth by the age of one year in black. The bars represent the number of individuals for each count of ‘delayed tooth eruption’ alleles. The line through points is a linear regression fit. doi:10.1371/journal.pgen.1000856.g002

Much as has been the case for genetic associations with height, another highly heritable and complex human trait, the variations the researchers linked with teething characteristics explain only a tiny fraction—about 3-4%—of the total variance seen in the population. More studies, with larger samples, will be needed in order to identify more SNPs, including those with smaller effect sizes and rare variants.

Based on the significant SNPs listed above, the authors defined a summary statistic called the “delayed tooth eruption measure,” which is calculated by adding up how many copies of the “delayed” version of each SNP a person carries. For women the total possible is 10 (two copies of each of five SNPs). Because one of the SNPs is on the X chromosome, for men the total possible is nine.

Based on the Finnish sample, the researchers calculated that individuals with a delayed tooth eruption measure of eight or more have an average of 1.5 fewer teeth at 12 months of age, and later tooth eruption by 1.1 months, compared to individuals with a score of three or less.

The researchers also evaluated whether or not any of the SNPs found in their study of infant teething were associated with the need for orthodontic treatment by age 31 in their Finnish sample. The only significant finding was a SNP that showed only suggestive evidence for an association with timing of first tooth eruption and number of teeth at age one (i.e., it is not in the table above). Each G at rs6504340 increased the odds of requiring orthodontic treatment by 1.35 times.

All of the SNPs identified in this study are in or around genes known to have roles in organ formation, growth and development, or cancer. The authors suggest that studies of teething and other aspects of infant development may have far reaching implications.

“The discoveries of genetic and environmental determinants of human development will help us to understand the development of many disorders which appear later in life. We hope also that these discoveries will increase knowledge about why fetal growth seems to be such an important factor in the development of many chronic diseases, ” said Professor Marjo-Riitta Jarvelin, the study’s senior author, in a press release.

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

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It may be you’ve heard a rumor that males are on the brink of extinction.

Whatever you may think of that prospect, the rumor is false. But over the past decade, numerous studies have hinted that the Y chromosome, a male necessity, is going the way of the dodo.

Though other studies have suggested this idea may be a bit of an exaggeration, a new report this week suggests that the Y chromosome may indeed be endangered.

In most mammals, such as us humans, two chromosomes determine the sex of each individual organism:  the X and the Y.  If an individual’s cells contain two copies of the X chromosome, then they will be genetically female.  If they contain one copy of the X and another of the Y, they will be male.

Yet even though these aptly named sex chromosomes have a similar duty — to confer sex — the X and the Y could not be more different.  The most striking difference between the two is their size; the Y is less than half as big as the X, and contains only 78 genes, compared to the more than 2,000 found along the X chromosome.  The evolutionary history of the two sex chromosomes and the question as to why they are so different from each other has been the subject of heated debate for many years.  Now scientists at Pennsylvania State University believe they’ve found a way to uncover not only the difference between the X and Y, but how and why it arose and what this means for the future of the small, but essential, Y chromosome.  Their results are reported in the July 17 issue of PLOS Genetics.

The research team, led by biologists Kateryna Makova and Melissa Wilson, believes the key to understanding the origins and future of the Y chromosome lie in some of our most distant mammalian relatives.  There are three classes of mammals: egg-layers like the platypus, marsupials like the kangaroo, and the eutherians, which includes humans and thousands of other similar species.  While there are many differences between the three groups, one of the most striking is the difference in the organization of the sex chromosomes.  As Makova explained, “In eutherian mammals, the sex chromosomes contain an additional region of DNA whereas, in the marsupials and egg layers, this additional region of DNA [is not on a distinct chromosome, but] is [a region of] the non-sex chromosomes.”

The authors argue that the key to the origins of the X and the Y chromosomes may lie in this fundamental difference.  By analyzing the X and Y of humans compared to the sex-determining regions of marsupials and egg-laying mammals, Makova and Wilson found that the X and Y split from the other chromosomes about 80 to 130 million years ago.

But that is not all they found.  The authors also examined how fast the X and Y mutated over time, and noticed a startling change that occurred at about the same time as the split.  “Our research revealed that the Y-specific DNA began to evolve rapidly at the same time that the DNA region split into two entities, while the X-specific DNA maintained the same evolutionary rate as it had previously,” Makova explained.

In other words, as soon as the X and the Y split their own distinct chromosomes, the Y began to evolve much more quickly than its counterpart, mutating at a much higher rate with each new generation.  The faster the Y evolved, the faster its genes disappeared.  Whereas at one point the Y may have contained thousands of genes, that number has dwindled to the mere 78.

The disappearance of these genes over time and the small number of those remaining on the Y begs the question:  will the Y chromosome ever disappear entirely?  The authors believed this was an important question to answer as well, and began additional analysis to determine the fate of the Y.

Makova and Wilson reasoned that there must be some utility to the Y, or else it surely would have disappeared by now.  As Wilson states, “we know that a few of the genes on the Y chromosome are important, such as the ones involved in the formation of sperm … .  Although there is evidence that the Y chromosome is still degrading, some of the surviving genes on the Y chromosome may be essential.”  By performing additional tests, they found that there were indeed some genes on the Y that will probably never disappear entirely.  But they also found several genes that were already disappearing, and were likely to be gone many generations from now.

Some recent studies have produced evidence that the genes on the Y may not be disappearing as fast as was initially thought. But, according to Makova, the Y chromosome may not be out of the woods just yet. “We still think there is a chance that the Y chromosome eventually could disappear,” she says.  “[But] if this happens, it won’t be the end of males.”  Instead, she believes that a new pair of sex chromosomes will arise from the genome, latching on to those few remaining genes, keeping alive the genes necessary for male survival.

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