USMLE® Step 1 style questions USMLE
A novel disease is discovered in a small population that follows an X-linked recessive inheritance pattern. The trait affects 1/5000 men in the population. Which of the following describes the frequency of this disease in the female proportion of the population?
Inheritance patterns exam links
Content Reviewers:Rishi Desai, MD, MPH
Contributors:Pauline Rowsome, BSc (Hons), Sam Gillespie, BSc, Victoria S. Recalde, MD
Inheritance patterns are the different ways in which traits are passed from one generation to another.
Inheritance relies on homologous chromosomes, which come in pairs - one from mom and one from dad. Each chromosome has genes, which are regions of DNA that carry information for a specific trait.
And different versions of the same gene are called alleles.
As an example, brown eye color and blue eye color are both alleles for the eye color gene.
Each parent offers one allele of a gene, which can be either dominant represented with a capital letter, like big A, or recessive, represented with a lowercase letter, like little a.
It only takes one dominant allele for its trait to be expressed, whereas it takes two recessive alleles for its trait to be expressed.
Human somatic cells - so, all of the cells aside from the gametes - have 23 pairs of chromosomes; 22 somatic pairs and one sexual pair - adding up to 46 chromosomes in total.
For the sex chromosomes, a genetic female has two X chromosomes, while a genetic male has an X and Y chromosome.
All 46 of these chromosomes, along with the alleles they carry, segregate during meiosis - which is the process of making gametes.
Gametes only carry half the genetic information of the parent - so 23 chromosomes. Females require an egg and a sperm that are both “22, X”, whereas males require an egg that’s “22,X” and a sperm that’s “22,Y”.
Once the male and female gametes merge during fertilization, their alleles combine to give rise to one of three possible genotypes of the offspring, homozygous dominant - or AA -, heterozygous - or Aa - , and homozygous recessive - or aa.
This genotype determines a person’s features —or phenotype— such as hair color, or whether or not they have a genetic disease.
Genetic diseases develop when a gene doesn’t work well because of a mutation that affects one of the two alleles, and if the person has children these mutations can be inherited.
To get a quick picture of how different inheritance patterns work, we’ll use a pedigree - where we represent females with a circle and males with a square.
We’ll shade in the individuals with the disease - so it’s based on phenotype, not genotype.
When a mutation affects a dominant allele, it only takes one mutant copy to cause a disease - this is a dominant inheritance pattern.
However, if a mutation affects a recessive allele, it takes two mutant copies to cause a disease - this is a recessive inheritance pattern.
Now, when the mutant allele is on a somatic chromosome, it’s called autosomal inheritance, and when it’s on a sex chromosome, it’s called sexual inheritance.
Sexual inheritance is divided into X-linked inheritance - where the mutant allele is on the X chromosome - and Y linked inheritance - where the mutant allele is on the Y chromosome.
Finally there’s mitochondrial inheritance.
In addition to the 46 chromosomes in the nucleus, cells also have mitochondria which carry their own DNA.
When an egg and sperm come together,
the cytoplasm and organelles like mitochondria come from the egg.
So when looking at the pedigree of a family affected by mitochondrial disease, you can see that as a result, both males and females can develop mitochondrial diseases but only females can pass those diseases to their children.
So, let’s look at autosomal dominant inheritance, an example would be Huntington’s disease, where there’s a mutation resulting in a dominant allele on an autosome.
So both homozygous dominant people -(DD)- and heterozygotes - (Dd) - have the disease.
But, homozygous dominant people rarely reproduce because the disease is too severe.
So, most of the individuals that reproduce are heterozygotes.
So let’s say that we have an individual who’s heterozygous - or Dd and that the other parent doesn’t have the disease, so they’re homozygous - dd - .
Now, since the mutation is on an autosome, it doesn’t matter which parent has the disease.
Now let’s create a Punnett square.
The affected parent can make either mutant gametes, which carry the D allele, or normal gametes, with the d allele.
The healthy parent only makes normal gametes carrying the d allele.
When these gametes combine, the children have a 50% chance of being heterozygous Dd and having the disease and a 50% chance of being homozygous recessive - dd- and not having the disease.
In a family pedigree, the inheritance pattern would look like this, with affected members in every generation.
Usually a person with the disease has one affected grandparent, affected and unaffected uncles and aunts, one affected parent, and even affected and unaffected siblings.
In addition, the mutation can also appear spontaneously in a person who’s family isn’t affected.
Now, autosomal recessive diseases, like cystic fibrosis only occur when a person has two recessive alleles - or rr.
And heterozygotes with only one mutant allele - or Rr - are considered to be carriers of the disease, even though they don’t have the disease.
For example, if two parents are carriers for cystic fibrosis - they are both heterozygous Rr.
Let’s use a Punnett square again.
They make gametes that have the normal R allele, or the recessive mutant r allele.
So, their children have 25% chance of ending up homozygous dominant - RR - which means they don’t have cystic fibrosis, aren’t carriers so are healthy.
Inheritance patterns refer to the different ways in which traits are passed from one generation to another. There are three patterns of inheritance: autosomal dominant, autosomal recessive, and X-linked.
Autosomal dominant inheritance means that only one copy of the defective gene is necessary for the trait to be expressed. This pattern is seen in conditions such as Huntington's disease and Marfan syndrome.
Autosomal recessive inheritance means that two copies of the defective gene are necessary for the trait to be expressed. This pattern is seen in conditions such as cystic fibrosis and sickle cell disease.
X-linked inheritance means that the gene is located on the X chromosome. Males have only one X chromosome, so they will express a disease if it is carried on that chromosome. Females have two X chromosomes, so they will only express a disease if they inherit two defective copies of the gene (one from each parent). This pattern is seen in conditions such as hemophilia and color blindness.