For those of you who are interested in the "sciency" side of DNA, Genie Judy Stanley sends this article from Atlantic magazine.
It’s Possible to Inherit More DNA From One Parent Than
the Other
23andMe’s 4-million-person database reveals
how many people are living with undetected chromosomal anomalies.
OCTOBER 10, 2019
Before
Natalie Nakles was born, before the egg from which she was conceived was even
fully mature, something went slightly awry. The egg that would help form her
ended up with two copies of chromosome 16. So today, 24-year-old Nakles does
not, as most people do, have one set of chromosomes from each parent. She has
two copies of chromosome 16 from her mother and none from her father.
This
phenomenon, called uniparental disomy, can happen in any of the 23 pairs of
chromosomes. In the scientific literature, it has been linked to spontaneous
abortions—and if the fetus survives, skeletal abnormalities, seizures,
intellectual disability, and childhood cancers. Nakles has Asperger’s syndrome,
but she is otherwise healthy. She has no serious health issues. She only found
out about her uniparental disomy after sending in her saliva to 23andMe.
Now a new study of DNA from 4.4
million 23andMe customers—as well as 430,000 people in the U.K. Biobank—suggests many other healthy people, like
Nakles, are living with uniparental disomy. The study identified 675 such
people and found no significant associations with deleterious traits.
Uniparental disomy is both more common and less detrimental than the scientific
literature suggested.
The
people in 23andMe and U.K. Biobank, on the other hand, skew healthy, and it
turns out that even healthy people can have what might seem to be big genetic
anomalies. “I like to say it’s normal to be abnormal,” Robinson says. She adds
that uniparental disomy sometimes comes up in prenatal tests, and the results
can make parents anxious because the existing scientific research is
essentially a catalog of everything that can go wrong. This study might add
some reassurance. “Just because you have that doesn’t automatically mean
there’s going to be anything wrong with your child,” she says.
Uniparental
disomy is the result of an error during meiosis, the process that forms eggs
and sperm. Scientists have proposed different mechanisms, but the most common
scenario probably goes like this: The error in meiosis gives the egg or sperm
an extra copy of one chromosome, so the resulting embryo ends up with three
copies on it. Sometimes, these embryos are spontaneously aborted, but other
times, they are able to go through “trisomy rescue,” in which some cells lose
that extra third chromosome and eventually outcompete the non-normal cells. The
resulting child ends up with the right number of chromosomes, but not
necessarily one from each parent.
This is all much more complicated than the standard story of sperm
meets egg, yet the result is still a healthy child. “It goes against so many of
the rules of biology you’ve memorized in school,” says Priyanka Nakka, a
postdoctoral fellow at Boston Children’s Hospital and former 23andMe intern who
co-wrote the study. Scientists have theorized and later discovered other ways
that conception can go very much awry yet still result in healthy children,
such as sesquizygotic twins.
When uniparental disomy
does lead to health problems, it is for one of two reasons. First, a child
might inherit two copies of a rare, recessive mutation from one parent. Second,
some genes are normally turned off or on depending on which parent they’re
inherited from in a phenomenon called “genomic imprinting.” That means
inheriting two copies from the same parent can cause various health issues. For
example, two maternal copies of chromosome 15 leads to Prader-Willi syndrome;
two paternal copies leads to Angelman syndrome. They are distinct genetic disorders
with very distinct symptoms.
Genomic
imprinting does not appear to be spread evenly across all chromosomes though,
and uniparental disomy is more serious when on some chromosomes than others.
Nakka and her co-authors found that most of the existing papers on uniparental
disomy focused on disorders related to chromosomes 6, 7, 11, 14, and 15. But
uniparental disomy among relatively healthy people in 23andMe and U.K. Biobank
tended to be more common on chromosomes 1, 4, 16, 21, 22, and X.
As
at-home DNA tests have become more common, customers have been discovering
uniparental disomies on their own. One prominent genetic genealogist, CeCe
Moore, told me she had seen about a dozen cases from people who had approached
her about their unusual DNA test results. 23andMe doesn’t flag uniparental
disomy to customers—and the company says it doesn’t plan to—but it’s possible
to deduce from closely scrutinizing the results.
Nakles figured it out after she and her mom both took 23andMe tests, and
she noticed they shared more of chromosome 16 than usual. She got her dad to
take a test, too, and it confirmed they shared no segments of chromosome 16 at
all. Nakles is a medical student, and she quickly pieced together how she came
to be in cellular detail. When we talked, she traced for me the initial error
in meiosis and the trisomy rescue that “fixed” it. She marveled at how easily
she could have not been born at all.
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