Would you like to know one of the most under appreciated pieces of cytoplasm out there? Platelets. We take for granted the function of our platelets, which are fragments of cells that help stop us from bleeding. They help our blood to clot when we get hurt. But there is a disorder called hemophilia that can affect those platelets and therefore the ability of blood to clot. With hemophilia, even a small cut could be dangerous because the bleeding can be continuous. There are now many good treatments for the symptoms of Hemophilia that have greatly improved outcomes with this disorder. Although it wasn’t always that way. Hemophilia is a sex-linked, recessive trait which means it is different from general Mendelian genetic problems. With sex-linked traits, we still use the terms dominant and recessive for alleles---except this time---those alleles are on sex chromosomes. This is the case with sex-linked traits. What is a sex chromosome? Well, first take a look at this karyotype which shows a human’s chromosomes. This karyotype has 46 chromosomes – arranged here in 23 pairs. 46 is the general number of chromosomes in humans but as we mention in our karyotype video, individuals can have more or fewer than 46. Chromosomes are made up of DNA and protein. They contain your genes. 23 of this person’s chromosomes came from an egg cell and 23 of this person’s chromosomes came from a sperm cell. The last two of the 46 chromosomes in this karyotype are called sex chromosomes. The sex chromosomes are commonly called X or Y chromosomes but X and Y has nothing to do with the shape of the chromosome. The reason for the X and Y names is really interesting---check out our further reading to learn more. All humans have at least one X chromosome. In most cases, females have a combination of XX and males have a combination of XY - but individuals can also have additional or fewer sex chromosomes. We’re focusing on sex chromosomes in this video because we’re going to show how to do Punnett squares with traits on those chromosomes. In the case of Punnett squares with sex-linked traits, the traits being tracked tend to be on the X chromosome and not the Y chromosome. The X chromosome is much larger than the Y chromosome and contains more genes than the Y chromosome. So technically, this video will be about X-linked traits but we do want you to know there are Y-linked traits, too. They exist. Referring back to the beginning when we mentioned the disorder hemophilia – hemophilia is a recessive sex-linked disorder, carried on the X chromosome. So focusing on that, let’s learn how to solve a Punnett square that involves this trait. We will use the capital letter “H” to represent an allele for not having hemophilia and a lowercase letter “h” to represent an allele for having hemophilia. Why? We’re going to do that because we mentioned hemophilia is a recessive sex-linked disorder, which is why it is being represented by a lowercase letter h. Only, it must be placed on the X chromosome as a superscript. Like an exponent. Let me explain what I mean by that. Let’s consider a female individual – shown with XX here. If the genotype is XHXH or XHXh, this female will not have hemophila. Why? Because as long as there is at least one dominant allele---that dominating allele---will be what shows in this trait. So no hemophilia. Hemophilia is a sex-linked RECESSIVE disorder. However, the XHXh genotype would be a carrier- meaning while the person wouldn’t have hemophilia, they would be carrying the recessive allele. The only way for this particular female to have hemophilia would be the genotype XhXh. Because only when there is no dominant present--- will that recessive show up, at least in this type of trait. Let’s consider a male individual – shown with XY here. XHY would be a genotype of a male without hemophilia. Notice how I didn’t put anything on the Y chromosome---again, most sex linked traits are on the X chromosome. If this male had the genotype XhY, then this individual would have hemophilia. Since there aren’t two X chromosomes for this person, either this person has hemophilia or doesn’t. Let’s try a Punnett square problem with this trait. Let’s say these two people here both do not have hemophilia although this female is a carrier of hemophilia. If they together have a biological child, what is the percent chance of the child having hemophilia? Also give genotype and phenotype ratios. Step 1) Always determine the genotypes of the parents first. This female must be XHXh. Why? The Punnett square problem says the individual doesn’t have hemophilia but is a carrier. That means this heterozygous genotype! It says the male does not have hemophilia and so the genotype must be XHY. If it was a lowercase “h,” this male would have hemophilia. Step 2) Place one parent’s genotype on the top, outside of the square like this. Place the other parent’s genotype on the left, outside of the square, like this. Step 3) Fill in the square! For formatting purposes, place X chromosomes before Y. You also write any sex chromosomes with dominant letters first. The results you get in the squares would be the offspring---the babies. The genotype ratio could be written out like this. And the phenotype ratio—remember that these are the traits---can be written out like this. There's a 75% chance that a child will be born without hemophila and a 25% chance that a child would have hemophilia, for this male here. Remember, like all punnett squares, these are representing probabilities. So because it’s a probability and not necessarily the exact outcome; they could for example have quadruplets that all do not have hemophilia or they could have quadruplets that all have hemophilia. The probability of the latter is less likely but it’s still possible. Five things to keep in mind when you are working these kind of Punnett squares: Number 1: You do not want to just assume a trait is a sex-linked trait, because many traits are not sex-linked. More traits are found on the autosomes actually. Autosomes are all the chromosomes that are not sex chromosomes. When you first started practicing with Punnett squares, it’s likely those were problems that were NOT sex-linked and thus the sex chromosomes of the parents would be irrelevant on the square. So never assume; the problem should indicate it’s a sex-linked trait in some way. Number 2: Did you notice how the child in our example that would have hemophilia was XY? Sex-linked recessive traits are more common in XY genotypes compared to XX because XY has only one X chromosome. For example, some forms of colorblindness are sex-linked recessive - it is more common in males. When arranging a pedigree that is tracking a sex-linked recessive trait, it can be common to see a lot of shaded squares in the pedigree--- representing males that have the sex-linked recessive trait. You can learn more about pedigrees in our pedigree video! Number 3: You may be wondering: our example was a sex-linked recessive trait. But can there be sex-linked dominant trait? Yes! A sex-linked dominant trait means it would only take one dominant allele for the individual to have the trait. Let’s use a letter “D” to illustrate a hypothetical sex-linked dominant trait. If it was a sex-linked dominant trait, these two female genotypes would have the trait because again it only takes one capital letter – a dominant allele - to have this dominant trait. This female would not have the sex-linked dominant trait. This male would have the dominant sex-linked trait, and this male would not. Number 4: Because we talked about the inheritance of the disorder hemophilia and we also mentioned colorblindness, we do want to make sure you don’t leave with a misconception: not all disorders that have a genetic component follow a one gene kind of trait. In fact, many don’t. An example? We both talk about how we developed preeclampsia – a disorder that occurs during pregnancy or the postpartum period that can be life threatening to those that develop it. While current research is studying genes that could play a role in developing preeclampsia – like genes that impact the placenta or genes that involve the vascular endothelium – the cause of preeclampsia is overall still not well understood. Many disorders though that have a genetic component can have multiple genes interacting together and wouldn’t be something you could place in a general Punnett square. And these disorders can have external factors as well that are separate from genetics. Number 5: Our example was for humans. Humans are animals but many animals do not have X and Y sex chromosomes – for example, birds where it’s Z and W. Or some animals might have X and Y sex chromosomes but maybe they typically have 10 of them, like the platypus. More in our description. Well that’s it for the amoeba sisters, and we remind you to stay curious.