Genetic variations The Royal Disease

On March 27, 1884, one of Queen Victoria's sons fell down some stairs at a yacht club in southern France.
The accident was minor; Prince Leopold suffered nothing more than a few bumps and bruises. But the 31-year-old Duke of Albany had hemophilia, a disorder that prevents the blood from clotting. His injuries triggered massive internal bleeding. Within 24 hours he was dead.
Leopold was the first of Queen Victoria's descendants to die of hemophilia; but he wasn't the last. Once science had revealed the cause of the disease it became clear why - though Victoria never suffered from hemophilia herself, she carried a genetic mutation that causes the condition and passed it on to several of her offspring.
Hemophilia is a perfect example of how genetic diseases and traits can run in families, popping up across the generations in ways that appear random - but in fact are quite predictable.

The X Factor
Hemophilia almost always strikes males, for reasons that become clear once the genetics of the disease are known. Blood clotting requires the proper functioning of a gene that lies on the X chromosome. Women inherit two X chromosomes, one from each parent; but men get only one X, from their mothers. In lieu of a second X, their fathers give them a Y chromosome, which contains the genes that confer maleness.
That means women always inherit two copies of the blood-clotting gene, one from each parent. If one is faulty, the other will do the job just fine. But men get only a single version of the blood-clotting gene. If that one happens to be faulty, there is no backup.
In Queen Victoria's case, both of her parents appear to have had correctly functioning blood-clotting genes. But due to a copying error during reproduction one of hers was dysfunctional. Such spontaneous mutations are uncommon, but far from unheard of - they pop up in about one person out of 50,000.
Victoria passed her deficient blood-clotting gene to only one of her sons - the unfortunate Leopold. But she also passed it to two of her daughters, Beatrice and Alice.

The Next Generations
Leopold, Beatrice and Alice had 12 offspring in all. Leopold's boys were unaffected, because they got their X chromosomes - and thus their blood-clotting genes - from their mother. But two of Beatrice's sons and one of Alice's inherited the faulty version of the X. Alice's son Frederick died as a young boy after smashing through a window. Beatrice's son Leopold bled to death at the age of 32 during a knee operation. Maurice, her other hemophiliac son, escaped a similar fate only because he was killed instantly by an exploding shell during World War I.
On the female side, Leopold and his sisters had four daughters who inherited the faulty X chromosome and spread it widely through the royal houses of Europe. During the early 20th century princes of Spain, Prussia, Russia and Great Britain suffered from what became known as "The Royal Disease."

What about the royals of today? Oddly enough, Victoria's deficient blood-clotting gene never made it beyond the fourth generation. By sheer luck, none of Victoria's great-great granddaughters in Spain or Britain inherited it. In Prussia she had only great-great grandsons. And none of her Russian great-great granddaughters ever had any children; all four were murdered during the Bolshevik revolution.

Your Family
When you and other family members join 23andMe, you can use our tools to trace the inheritance of genes in your own pedigree. You can compare yourself with siblings or cousins to see which genes you both inherited from the same parent or grandparent. Though few inherited traits are as easily traced through a family tree as hemophilia.
23andMe's Family Inheritance tools can certainly help you explore some of your own family's distinctive characteristics.

visit: www.23andme.com

Genetic variations The Story of Muggsy Bogues

When Tyrone "Muggsy" Bogues was growing up, no one expected him to be an NBA star. At only 5' 3", Muggsy was short, putting him at a serious disadvantage in a league where the average height is 6' 7". But he ignored the naysayers, and went on to have a successful basketball career despite the odds stacked against him. During his 16-year career in the NBA, Muggsy became a fan favorite - a symbol of hard work, drive, and determination. "I always believed in myself," he told Hank Hersch of Sports Illustrated. "That's the type of attitude I always took out on the floor, knowing that I belonged; that with my talents, my abilities, there's a place for me out there."

The Genetics of Height

Height is determined partly by genes and partly by additional factors, such as whether a person had a healthy diet while growing up. But the genetics of height is complex. One recent study found that numerous genes influence a person's height [1]. The most conclusive study to date pinpointed an individual gene that influences the trait, but it accounts for only a centimeter of a person's stature - a tiny fraction of the total variation in human height [2]. As more studies are conducted, we will almost certainly discover more about the genetic basis of height.

Genetics is Not Your Destiny
The good news is, genetics isn't necessarily destiny. The story of Muggsy Bogues is a clear example of why genes alone cannot predict a person's effectiveness or success in a certain activity. Muggsy Bogues used his strengths - quickness, speed, and explosiveness - to his advantage.
When he was growing up, Muggsy and his friends practiced dunking using open-bottomed milk crates hung on the Baltimore playground fences. It was at high school where Bogues earned his catchy nickname, "Muggsy", a reference to his physical style of play.
Muggsy was a standout collegiate player at Wake Forest University, where he set an Atlantic Coast Conference record for assists. He was drafted in the first round of the NBA and led the Charlotte Hornets to the playoffs in 1992 and 1995. Following his NBA career, Muggsy went on to become the coach of a women's NBA team, the Charlotte Sting, where he was shorter than all of the female players he coached.
Muggsy's storied career demonstrates that with hard work and determination, you can beat the odds and accomplish your goals. As he once told the children's magazine Highlights for Children, "You can't dwell on what people think you can't do."

References:
[1] Visscher et al. (2007) "Genome partitioning of genetic variation for height from 11,214 sibling pairs." Amer J Hum Genet 81(5):1104-10.
[2] Weedon et al. (2007) "A common variant of HMGA2 is associated with adult and childhood height in the general population. Nat Genet 39(10):1245-1250.