Inheritance Patterns

There are three main mendelian inheritance patterns: autosomal dominant, autosomal recessive, and sex-linked.

Autosomal disorders

The term autosomal means that the gene causing the disorder is not on a sex chromosome, but is on chromosomes #1-22. You will see why we have to distinguish between sex and non-sex chromosomes when categorizing disorders in the section below. Imagine a disease is caused by the mutated gene “m” (lowercase) and the normal copy of the gene is written as “M” (uppercase). When drawing out inheritance patters you can use any letter, we have just picked “M” for our discussion here. With any autosomal genetic disorder, if you have two copies of the mutated form of the gene, you will always be affected with the disease. In the same way, if you have two copies of the normal form of the gene, you will not get the disease. Whether the disease is dominant or recessive only affects those people with one copy of the normal gene as well as one copy of the mutated gene. (Mm If the mutated form of the gene is dominant over the normal one, the person will be affected with the disorder because it is the abnormal form that overrides the normal one. However, if the mutated form of the gene is recessive, then the patient will not be affected by the disease because the normal gene overrides the abnormal one. In this case, the form of the gene that is dominant determines the outcome for the person.

Huntington disease is an example of a dominant disorder caused by a mutation in the huntington gene. Using the same letters from above with the normal huntington gene written as “M” and the mutated gene written as “m,” below are the possible genotypes and related phenotypes a person could have.

MM: the person has two copies of the normal gene, will not develop Huntington disease, and cannot pass a mutated gene onto children

mm: the person has two copies of the abnormal gene, will develop Huntington disease, and all children will inherit a mutated gene and also develop Huntington.

Mm: this person has one copy of the normal gene and one copy of the mutated gene. He/she will develop Huntington disease, and has a 50% chance of passing on the mutated gene to a child who would then also have the disease.

Cystic Fibrosis is an example of a recessive disorder caused by a mutation in the CFTR gene. Using the same letters from above and the normal CFTR gene written as “M” and the mutated gene written as “m,” below are the possible genotypes and related phenotypes a person could have.

MM: the person has two copies of the normal gene, will not have cystic fibrosis, and cannot pass a mutated gene onto children

mm: the person has two copies of the abnormal gene, will have cystic fibrosis, and all children will inherit a mutated gene and will all be carriers of cystic fibrosis. Only if their children also inherited a mutated gene from the other parent will they be affected.

Mm: this person has one copy of the normal gene and one copy of the mutated gene. He/she will not have cystic fibrosis, but is a carrier and therefore and has a 50% chance of passing on the mutated gene to a child making the child a carrier unless the child inherits another mutated gene from the other parent.

Sex-linked disorders

A sex-linked disorder is one that is caused by a gene located on a sex chromosome (X and Y chromosomes). As you know, females have two X chromosomes and males have one X and one Y chromosome.

Duchenne muscular dystrophy is an example of a recessive sex-linked disorder. This disease is caused by a mutation in the DMD gene found on the X chromosome. This means that females have two copies of the gene, while males only have one. Below are the genotypes and related phenotypes a person could have. The X and Y in front of the “M” signifies the chromosome that the gene is on.

X^M X^M: this is a female with two copies of the normal gene, she will not have muscular dystrophy and will not pass on a mutated gene to any children.

X^m X^m: this is a female with two copies of the mutated gene, she would have muscular dystrophy and our pass on a mutated gene to all children. However, this does not occur with duchenne muscular dystrophy because this female would have to have inherited a mutated gene from both parents. This would mean her dad would have had duchenne muscular dystrophy (XmY). Men with duchenne muscular dystrophy do not reproduce. There are other types of muscular dystrophy that are milder and men with those conditions can reproduce.

X^M X^m: this female has one copy of the normal gene and one copy of the mutated DMD gene. She will not develop duchenne muscular dystrophy because it is a recessive disease and she still has one functioning dominant gene. She is however a carrier and has a 50% chance of passing on the mutated gene to each child. Any male children who inherit the mutated gene will be affected. Any female children who inherit the mutated gene will not be affected but will be a carrier.

X^M Y: this is a male with a normal DMD gene. He will not develop duchenne muscular dystrophy and will not pass on a mutated gene to any children.

X^m Y: this is a male with a mutated DMD gene. He will be affected with duchenne muscular dystrophy. He will pass on that mutated gene to all female children but not male children (they will get his Y chromosome instead). Those female children who inherit a mutated gene will be carriers but not be affected with duchenne muscular dystrophy themselves. Note that men only have to have one mutated copy of the DMD gene for the disease to develop.

There are other X-linked disorders where carrier females can show some symptoms of the disorder and are called symptomatic carriers. Usually these symptoms are milder than what they are with the full disorder. An example of this is Hemophilia A and B. Hemophilia is a bleeding disorder caused by mutation in the F8 (Factor VIII) gene. The factor VIII protein is part of the clotting cascade and when it is not present, clots do not form well causing the person to bleed excessively. This disorder is inherited in the same way as duchenne muscular dystrophy discussed above. However, with hemophilia about 10% of carrier females are also at risk for bleeding but it is milder than it is in males.

Additional resources on inheritance patterns at: http://www.uvm.edu/~cgep/Education/Inheritance2.html.

“Human Pedigree Analysis.” Discover Biology 3rd Edition Animations. 2006. W. W. Norton and Company. 12 December 2008. http://www.wwnorton.com/college/biology/discoverbio3/full/content/index/animations.asp