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X-linked inheritance

AP.BIO:
IST‑1 (EU)
,
IST‑1.J (LO)
,
IST‑1.J.2 (EK)
Chromosomal basis of sex determination. X and Y chromosomes, X-linkage.

Key points:

  • In humans and other mammals, biological sex is determined by a pair of sex chromosomes: XY in males and XX in females.
  • Genes on the X chromosome are said to be X-linked. X-linked genes have distinctive inheritance patterns because they are present in different numbers in females (XX) and males (XY).
  • X-linked human genetic disorders are much more common in males than in females due to the X-linked inheritance pattern.

Introduction

If you’re a human being (which seems like a good bet!), most of your chromosomes come in homologous pairs. The two chromosomes of a homologous pair contain the same basic information – that is, the same genes in the same order – but may carry different versions of those genes.
Are all of your chromosomes organized in homologous pairs? The answer depends on whether you’re (chromosomally) male.
Image of a human karyotype, showing the 44 autosomes in matching pairs and 2 dissimilar sex chromosomes (X and Y),
Image modified from "Karyotype," by Can H. (CC BY 2.0).
  • A human male has two sex chromosomes, the X and the Y. Unlike the 44 autosomes (non-sex chromosomes), the X and Y don’t carry the same genes and aren’t considered homologous.
  • Instead of an X and a Y, a human female has two X chromosomes. These X chromosomes do form a bona fide homologous pair.
Because sex chromosomes don’t always come in homologous pairs, the genes they carry show unique, distinctive patterns of inheritance.

Sex chromosomes in humans

Human X and Y chromosomes determine the biological sex of a person, with XX specifying female and XY specifying male. Although the Y chromosome contains a small region of similarity to the X chromosome so that they can pair during meiosis, the Y chromosome is much shorter and contains many fewer genes.
To put some numbers to it, the X chromosome has about 800, minus, 900 protein-coding genes with a wide variety of functions, while the Y chromosome has just 60, minus, 70 protein-coding genes, about half of which are active only in the testes (sperm-producing organs)start superscript, 1, comma, 2, comma, 3, comma, 4, end superscript.
Diagram of the human X and Y chromosomes. The X is much larger than the Y. The X and Y have small regions of homology at both tips, which allow pairing of the chromosomes during meiosis. The SRY gene is found on the Y chromosome, near the tip, just below the region of homology with the X chromosome.
Image based on ideograms from the Genome Decoration Page, maintained by the U.S. NCBI.
The human Y chromosome plays a key role in determining the sex of a developing embryo. This is mostly due to a gene called SRY (“sex-determining region of Y”). SRY is found on the Y chromosome and encodes a protein that turns on other genes required for male developmentstart superscript, 5, comma, 6, end superscript.
  • XX embryos don't have SRY, so they develop as female.
  • XY embryos do have SRY, so they develop as male.
In rare cases, errors during meiosis may transfer SRY from the Y chromosome to the X chromosome. If an SRY-bearing X chromosome fertilizes a normal egg, it will produce a chromosomally female (XX) embryo that develops as a malestart superscript, 7, end superscript. If an SRY-deficient Y chromosome fertilizes a normal egg, it will produce a chromosomally male embryo (XY) that develops as a femalestart superscript, 8, end superscript.

X-linked genes

When a gene is present on the X chromosome, but not on the Y chromosome, it is said to be X-linked. X-linked genes have different inheritance patterns than genes on non-sex chromosomes (autosomes). That's because these genes are present in different copy numbers in males and females.
Since a female has two X chromosomes, she will have two copies of each X-linked gene. For instance, in the fruit fly Drosophila (which, like humans, has XX females and XY males), there is a eye color gene called white that's found on the X chromosome, and a female fly will have two copies of this gene. If the gene comes in two different alleles, such as start text, X, end text, start superscript, W, end superscript(dominant, normal red eyes) and start text, X, end text, start superscript, w, end superscript (recessive, white eyes), the female fly may have any of three genotypes: start text, X, end text, start superscript, W, end superscriptstart text, X, end text, start superscript, W, end superscript (red eyes), start text, X, end text, start superscript, W, end superscriptstart text, X, end text, start superscript, w, end superscript (red eyes), and start text, X, end text, start superscript, w, end superscriptstart text, X, end text, start superscript, w, end superscript (white eyes).
A male has different genotype possibilities than a female. Since he has only one X chromosome (paired with a Y), he will have only one copy of any X-linked genes. For instance, in the fly eye color example, the two genotypes a male can have are start text, X, end text, start superscript, W, end superscript, start text, Y, end text (red eyes) and start text, X, end text, start superscript, w, end superscript, start text, Y, end text (white eyes). Whatever allele the male fly inherits for an X-linked gene will determine his appearance, because he has no other gene copy—even if the allele is recessive in females. Rather than homozygous or heterozygous, males are said to be hemizygous for X-linked genes.
We can see how sex linkage affects inheritance patterns by considering a cross between two flies, a white-eyed female (start text, X, end text, start superscript, w, end superscript, start text, X, end text, start superscript, w, end superscript) and a red-eyed male (start text, X, end text, start superscript, W, end superscript, start text, Y, end text). If this gene were on a non-sex chromosome, or autosome, we would expect all of the offspring to be red-eyed, because the red allele is dominant to the white allele. What we actually see is the following:
This illustration shows a Punnett square analysis of fruit fly eye color, which is a sex-linked trait. A red-eyed male fruit fly with the genotype X^{W}Y is crossed with a white-eyed female fruit fly with the genotype X^{w}X^{w}. All of the female offspring acquire a dominant W allele from the father and a recessive w allele from the mother, and are therefore heterozygous dominant with red eye color. All of the male offspring acquire a recessive w allele from the mother and a Y chromosome from the father and are therefore hemizygous recessive with white eye color.
Image credit: "Characteristics and traits: Figure 10," by OpenStax College, Biology, CC BY 4.0
However, because the gene is X-linked, and because it was the female parent who had the recessive phenotype (white eyes), all the male offspring—who get their only X from their mother—have white eyes (start text, X, end text, start superscript, w, end superscript, start text, Y, end text). All the female offspring have red eyes because they received two Xs, with the start text, X, end text, start superscript, W, end superscript from the father concealing the recessive start text, X, end text, start superscript, w, end superscript from the mother.

X-linked genetic disorders

The same principles we see at work in fruit flies can be applied to human genetics. In humans, the alleles for certain conditions (including some forms of color blindness, hemophilia, and muscular dystrophy) are X-linked. These diseases are much more common in men than they are in women due to their X-linked inheritance pattern.
Why is this the case? Let's explore this using an example in which a mother is heterozygous for a disease-causing allele. Women who are heterozygous for disease alleles are said to be carriers, and they usually don't display any symptoms themselves. Sons of these women have a 50, percent chance of getting the disorder, but daughters have little chance of getting the disorder (unless the father also has it), and will instead have a 50, percent chance of being carriers.
A diagram shows an unaffected father with a dominant allele and an unaffected carrier mother with an x-linked recessive allele. Four figures of offspring are shown representing the various resulting genetic combinations: unaffected son, unaffected daughter, affected son, and unaffected carrier daughter.
Image credit: "Characteristics and traits: Figure 10," by OpenStax College, Biology, CC BY 4.0
Why is this the case? Recessive X-linked traits appear more often in males than females because, if a male receives a "bad" allele from his mother, he has no chance of getting a "good" allele from his father (who provides a Y) to hide the bad one. Females, on the other hand, will often receive a normal allele from their fathers, preventing the disease allele from being expressed.

Case study: Hemophilia

Let's look at a Punnett square example using an X-linked human disorder: hemophilia, a recessive condition in which a person's blood does not clot properlystart superscript, 13, end superscript. A person with hemophilia may have severe, even life-threatening, bleeding from just a small cut.
Hemophilia is caused by a mutation in either of two genes, both of which are located on the X chromosome. Both genes encode proteins that help blood clotstart superscript, 14, end superscript. Let's focus on just one of these genes, calling the functional allele start text, X, end text, start superscript, H, end superscript and the disease allele start text, X, end text, start superscript, h, end superscript.
In our example, a woman who is heterozygous for normal and hemophilia alleles (start text, X, end text, start superscript, H, end superscript, start text, X, end text, start superscript, h, end superscript) has children with a man who is hemizygous for the normal form (start text, X, end text, start superscript, H, end superscript, start text, Y, end text). Both parents have normal blood clotting, but the mother is a carrier. What is the chance of their sons and daughters having hemophilia?
Punnett square showing the potential genotypes of children produced by a father with normal clotting (start text, X, end text, start superscript, H, end superscript, start text, Y, end text) and a heterozygous carrier mother (start text, X, end text, start superscript, H, end superscript, start text, X, end text, start superscript, h, end superscript).
start text, X, end text, start superscript, H, end superscriptstart text, Y, end text
start text, X, end text, start superscript, H, end superscriptstart text, X, end text, start superscript, H, end superscript, start text, X, end text, start superscript, H, end superscriptstart text, X, end text, start superscript, H, end superscript, start text, Y, end text
start text, X, end text, start superscript, h, end superscriptstart text, X, end text, start superscript, H, end superscript, start text, X, end text, start superscript, h, end superscriptstart text, X, end text, start superscript, h, end superscript, start text, Y, end text
All daughters (start text, X, end text, start superscript, H, end superscript, start text, X, end text, start superscript, H, end superscript, start text, X, end text, start superscript, H, end superscript, start text, X, end text, start superscript, h, end superscript) have normal blood clotting because they have at least one start text, X, end text, start superscript, H, end superscript alelle. 1, slash, 2 of the daughters are carriers, while the other half are homozygous for the start text, X, end text, start superscript, H, end superscript allele.
1, slash, 2 of sons are start text, X, end text, start superscript, H, end superscript, start text, Y, end text and have normal blood clotting.
1, slash, 2 of sons are start text, X, end text, start superscript, h, end superscript, start text, Y, end text and have hemophilia.
Since the mother is a carrier, she will pass on the hemophilia allele (start text, X, end text, start superscript, h, end superscript) on to half of her children, both boys and girls.
  • None of the daughters will have hemophilia (zero chance of the disorder). That's because, in order to have the disorder, they must get a start text, X, end text, start superscript, h, end superscript allele from both their mother and their father. There is 0 chance of the daughters getting an start text, X, end text, start superscript, h, end superscript allele from their father, so their overall chance of having hemophilia is zero.
  • The sons get a Y from their father instead of an X, so their only copy of the blood clotting gene comes from their mother. The mother is heterozygous, so half of the sons, on average, will get an start text, X, end text, start superscript, h, end superscript allele and have hemophilia (1, slash, 2 chance of the disorder).

Check your understanding

  1. Which of the following pairs of parents is most likely to produce a daughter with hemophilia?
    Choose 1 answer:


Want to join the conversation?

  • aqualine seed style avatar for user Wonton says hi!
    In the second paragraph of the section titled "Sex Chromosomes in Humans", do Chromosomally female (XX) embreyos that develope into males make them have a more girlish appearance? Do Chromosomally male (XY) embreyos that develope into females make them have a more boyish appearance? Some boys might look a lot like girls or vice versa.
    (9 votes)
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  • blobby green style avatar for user abbyacevedo21
    What is Gene-linkage? How is it different from the Sex-Linkage?
    (5 votes)
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  • blobby green style avatar for user Priyanka
    "SRY is found on the Y chromosome and encodes a protein that turns on other genes required for male development.

    If an SRY-bearing X chromosome fertilizes a normal egg, it will produce a chromosomally female (XX) embryo that develops as a male."
    So, the SRY induces other genes to produce male character.
    Does that mean that the X chromosome also contains other genes that are required for male development?(genes that would be dormant in the absence of SRY)
    (6 votes)
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    • female robot grace style avatar for user tyersome
      I'm not an expert on this, but my understanding is that SRY† is (usually) sufficient for embryonic testis formation and that the hormonal effects of having testis are (usually) sufficient for male primary and some secondary sexual traits§. One way of looking at this is that male and female sexual anatomy aren't as different as they appear, they just have different structures emphasized and elaborated with a few small changes in "plumbing".

      UPDATE:
      †Note: SRY encodes TDF (testis determining factor) a transcription factor that enhances expression of genes needed for testis development and possibly suppresses expression of genes that promote ovary development. This is an active area of research and there is evidence that SRY is not always necessary for male development and also may not always be sufficient for male development.
      If you want to learn more about this, here is a good (and freely available) review article:
      https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001899

      §Note: Some other genes on the Y chromosome are necessary for sperm production, but they don't appear to be needed for "maleness".
      (5 votes)
  • blobby green style avatar for user Sk Nigam
    all the x linked alleles a man has come from his mother
    (3 votes)
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  • piceratops ultimate style avatar for user INonDeficere
    Is it impossible to have parents with twelve kids that pass on an infected trait to 6 of the males and 1 female. I was given this problem on another site and got it wrong when I said no. Help!
    (1 vote)
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    • duskpin tree style avatar for user Natrium Chloride
      The question didn't mention that it is X-linked or Y-linked, so you cannot assume it is sex linked. (Or perhaps it did, but as you didn't mention, then I'd assume the question didn't)

      The only way for a pair of unaffected parents to have affected offspring is for the allele for the disease to be recessive, both parents must have a dominant allele and parents must be heterozygous so they have a dominant allele. To have a heterozygous male, the allele cannot be on the non-homologous portion of the X chromosome. (Note that this doesn't mean it cannot be on the X chromosome.)
      *Also I want to mention that as the question asks whether it is possible to have 6 affected males and 1 affected female, but does not state that there are that number of affected males and females. Therefore @Anson Chan you cannot prove the allele is recessive by that. And it did not mention how many female and male offspring they have in total, and this is not important. It is sometimes fatal to assume something the question has not said, even though in this case, there isn't much difference.
      **Idk if I sound harsh, bu no offence. I am just trying to share my experience

      Back to the question, in the case I just mentioned (heterozygous parents for the disease caused by recessive alleles) it is possible for 6 males and 1 female to have the disease if they inherit both recessive alleles from both parents.

      As the aforementioned case suits the situation of the question completely, the answer is yes.
      ------------
      Now I have finished explaining this question, let's go for something extra.

      So this situation can happen when the locus of this allele is on a pair of autosomes.

      Now let's assume there are six boys and six girls among the offspring. (You cannot assume this when solving the question because it's not mentioned, but as a case study, we'll assume this. And don't worry, it is a possible case)

      Now the rate of the male offspring getting the disease is 100% while that of female offspring is just 16.7%. Why the great difference? One possibility is that the allele is on the homologous portion of the sex chromosomes. The allele from the father is on his Y chromosome. Therefore the rate of male offspring getting the disease is much larger. Then why does one girl get the disease? That's because crossing over may occur and the allele causing the disease shifted to the X chromosome of the sperm that.

      Anyway, this whole case isn't very likely because for the male offspring, even if they all receive the defective chromosome from the father, there is still half the chance they receive a dominant good allele from their mother.

      Happy learning to all of you!
      (2 votes)
  • aqualine tree style avatar for user abbykbarr1
    so I know a little boy who has three chromosomes. He has an Xyy chromosomes. What does that mean and how does that affect him?
    (3 votes)
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  • blobby green style avatar for user Emily James
    It says in the 2nd paragraph of 'sex chromosomes in humans' that the X chromosome has 800-900 protein-coding genes while the Y chromosome has only 60-70, half of which are responsible for roughly the same task or processes in the same area. How does the male genome make up for that lack of proteins? Are they just not needed or are they found somewhere else? Surely the second X chromosome in females carries something which would be important in males too.
    (2 votes)
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  • blobby green style avatar for user Jeffery Blaha
    Curious to know what formula would be used to try and determine the likelihood of having "X" number of children (i.e.5) in a row that could be affected or unaffected. I understand the initial Punnet Square probabilities, I just am trying to figure out how to determine "future" probabilities.
    (1 vote)
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    • leaf grey style avatar for user Justin Watson
      I believe you basically treat it like any other probability and you multiply the chance of one event by the number of events. For instance:

      If the chance of the parents having a normal-vision child (versus a colorblind child) is 75%, so the odds of the parents having 3 healthy children (not counting triplets, just three separate events) would be 75% x 75% x 75%. I believe the final answer would roughly 42%.
      (4 votes)
  • male robot donald style avatar for user Regan Smallacombe
    Are there any Y-linked genetic disorders?
    (0 votes)
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  • leafers tree style avatar for user Monica
    It says that females have two X chromosomes and therefore they are much less likely to get an X-linked recessive disorder. Since one of the X chromosomes in females inactivate (forming a Barr body) during development, what if a female was a carrier and the X chromosome with the dominant allele was inactivated? Would they express the recessive allele and have the disorder? Thank you!:)
    (2 votes)
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