by Marina Watanabe
figures by Elayne Fivenson

Hours after giving birth, my sister sent a picture of her newborn baby to our family group text. In what I can only assume was a painkiller-induced haze, she wrote, “The baby looks exactly like me!!!”

The baby did not look exactly like her.

The baby, like all newborn babies, looked exactly like a potato.

This idea of children being “mini mes” of their biological parents is a common conversation piece, and people often joke that the child is a clone of one parent or the other. Despite these jokes, it’s generally understood that it takes two to make a baby (for the most part!!) and that half the baby’s DNA comes from an egg and half from a sperm. But sometimes, a real “mini me” is born with the majority of DNA coming from only one parent.

Family matters

In the Czech Republic, a deaf nine year old child underwent genetic testing to try to pinpoint the cause of the deafness. Apart from the length and width of the patient’s legs slightly differing, there were no features to mark the child as being particularly out of the ordinary. The genetic testing results showed that the patient had two copies of a specific mutation, or alteration, in the genetic code. Interestingly, though, the mutation in question was not thought to cause deafness. 

To begin unraveling the mystery of the relationship between the mutation and the patient’s deafness, the doctors tracked the mutation within the family. Classical genetics states that since the patient had two mutant copies of the gene, both parents must also have the mutation and they both must have passed it onto their child. The parents underwent genetic testing and it was determined in a bizarre twist that only the father had the mutation. Before things could derail into a confusing and seemingly impossible game of “Who’s the Mommy?!,” the doctors did further genetic testing to reach a jarring conclusion: The patient’s DNA was almost exclusively from the father. Also, I forgot to mention–the patient is a girl.

How we inherit genetic material from our biological parents  

DNA is the instruction manual of what makes you who you are, and it is found in your body in the form of 23 pairs of chromosomes (for a total of 46 chromosomes). You got one set of 23 chromosomes from one parent inside a sperm, and the other 23 from the other parent inside an egg. Because we have two copies of our DNA, humans are what’s known as “diploid” and this is annotated as “2n.”  Almost all the cells in your body contain a copy of this full set of 23 pairs of chromosomes you got from your biological parents. The exception are gametes, which are sex cells (sperm or eggs), that only contain 23 chromosomes—not 46. Since they only contain one copy of our genetic information, gametes are 1n instead of 2n. 

 Normally, the creation of gametes in an adult male or female is very straightforward (Figure 1).  For each chromosome, you start with the full set consisting of two copies—one from each parent.  Through a process called meiosis, these two chromosomes duplicate themselves (so you end up with four copies of each chromosome) and ultimately split into four gametes containing only one of each chromosome–meaning each gamete contains only half the amount of DNA required for a human. This “halving” process occurs simultaneously across all 46 chromosomes, leading to the production of many gametes containing 23 chromosomes each. After meiosis, a sperm and an egg are then free to combine their incomplete genetic material to create a genetically complete cell known as a zygote. This single-celled zygote is what grows into a new human.

Figure 1: Classical gamete formation. Parent 1 (blue cells) and Parent 2 (red cells) both start with a complete pair of chromosomes (2n), duplicate their chromosomes (4n), and eventually end up with four gametes that contain half the normal number of chromosomes (1n). When two 1n gametes from two different individuals combine together, a zygote (2n) is formed. For simplicity’s sake, only one set of chromosomes is depicted, but this normally takes place across all 23 pairs of chromosomes simultaneously.

Redefining single parenting 

In the case of the nine year old girl, she did not receive the normal half and half ratio of DNA from her parents. Though the doctors were trying to diagnose the cause of her deafness, they instead diagnosed her with genome-wide uniparental disomy or diploidy (GWUPD). In this condition, a person will not inherit 23 chromosomes from one parent each for a total of 46, but will instead inherit almost all chromosomes from one parent. In this way, one person is essentially both biological “mother” and “father” to a child. This is an incredibly rare condition, and as of 2018, only approximately 21 cases have been reported

A curious feature of GWUPD is the fact that all of the patients affected are girls and women who have inherited mostly their father’s genetic material. The reason why the single genetic parent has thus far always been the father is not yet known due to the fact that the condition is so rare and it is experimentally difficult to understand a process that is taking place in the very early zygote. 

Though scientists still do not fully understand GWUPD or its causes, they do have a theory (paywall). They believe that, much like in classical zygote formation (Figure 1), a sperm and egg met to form a zygote. At this point, both the DNA from the sperm and the DNA from the egg should have begun replicating themselves so that the one-celled zygote could begin making more and more cells with both sets of DNA in order to create a fully-functioning human embryo (Figure 2a). However in the case of GWUPD, for whatever reason, the genetic information from the mother did not replicate properly, leading to two populations of cells–those with DNA from both parents and those with DNA only from the father (Figure 2b). 

Figure 2: Zygote replication. A) In classical development, the genetic source material from both parents are faithfully replicated and all resulting cells that will make up the embryo have DNA from both parents. B) In GWUPD patients, it is theorized that the genetic material from the egg does not replicate. Thus, resulting cells may or may not contain maternal DNA. In those 1n cells that only contain one copy of paternal DNA, the lonely genetic information will undergo a process known as “haploid rescue.” This process is truly as dramatic and heroic as it sounds and consists of the paternal DNA replicating itself to go from being a 1n cell to 2n. For simplicity’s sake, only one set of chromosomes is depicted, but this process normally takes place across all 23 pairs of chromosomes simultaneously.

In GWUPD patients, these different cells with different chromosomes go on to compose different parts of the body so that, depending on the tissue, the genetics may vary. For example, in the case of the nine year old Czech girl, the percentage of cells containing only her father’s DNA was 93% in her blood but 74% in her saliva. So while she is mostly composed of her father’s genetic material, she does still have some of her mother in her. 

Side effects may vary 

GWUPD patients often have high levels of insulin, asymmetrical body parts, seizures, severe developmental delays, are born prematurely, and/or are more susceptible to developing cancer. Since each patient derives their DNA from their individual and unique parent, the genetics of the patients vary wildly from one to the other and their symptoms vary. One of the reasons why the case of the Czech girl was so interesting to doctors was the fact that she did not present with most of these common symptoms, but instead exhibited only deafness and asymmetric legs. Although they followed her for three years (publishing the paper about her when she was 11), her doctors were unable to determine the cause of her deafness.

Stranger than fiction

We sometimes assume that creating a human life is a simple and straightforward process. However, when we see patients with GWUPD, we understand just how easily the process of creating new life can go awry. The creation of a daughter from just a man’s genetic information sounds like something from Science Fiction (and has actually been the basis for an episode of Doctor Who!), but it is a phenomenon that very much exists and can have very negative consequences. While we may joke that a child is their parent’s “mini-me,” it is interesting to note that this is an actual possibility in the world of biology. Having “too much” DNA from one parent might not seem like a problem in and of itself, but it is proof that genetic diversity is important for life.   

Figure 3: All babies look the same. Me (left) and my niece (right) at roughly the same age. These photos prove my completely informed and wise stance that all babies look like potatoes (and thereby each other??) but probably not their parents. Haters gonna hate. Potatoes gonna potate.

 


Marina Watanabe is a PhD candidate in the Biological and Biomedical Sciences graduate program at Harvard University. She loves her potato niece very much.

Elayne Fivenson is a third-year Ph.D. student in the Biological and Biomedical Sciences program at Harvard Medical School, where she is studying the genetics and biochemistry of the bacterial cell envelope

Cover image: “Karyotype of a human male”

For More Information:

  • Read about this interesting case (paywall) of a patient with mostly maternal DNA who has cells that are XX (biologically female) or XY (biologically male) depending on where they are sampled from. 
  • Uniparental disomy is GWUPD on a small scale where only one chromosome pair or part of a chromosome pair comes from one parent. This is very different from GWUPD where almost all of the chromosomes come from one parent.
  • See this Khan Academy page for an introduction to classical genetics and inheritance
  • This Khan Academy link covers meiosis and how it leads to genetic diversity. Lessons on this page explain a process called “recombination” that ensures genetic diversity in offspring. Recombination explains why siblings are genetically different from each other even though they share the same parental “source material” and why GWUPD patients cannot be regarded as clones of their fathers.

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