0305 - Inherited Disorders - RM Flashcards
What is Cystic Fibrosis? How is it caused?
Cystic Fibrosis is a recessive disease that largely effects lung function due to abnormal chloride and sodium levels in the epithelium. It is caused by a mutation in the gene CFTR (Cystic Fibrosis Transmembrane Conductance Regulator). Around 1500 different mutations can lead to the phenotype of CF.As it is a recessive disorder, both parents must be carriers (Aa), with the child having a ¼ chance of the phenotype.
What is Huntington’s Disease? How is it caused?
Huntington’s Disease is a dominant autosomnal (non sex-linked) disease that causes uncontrollable limb movements and dementia. Symptoms do not normally present until later in life, however it can be easily genetically identified any time. It occurs on the Huntingtin gene on C4, which has an unknown main role, but is essential for development and plays a role in nerve function.The severity of Huntington’s disease, and the age of onset, is determined by the number of CAG expanded repeats on the gene. In males, this progresses through generations, with earlier onset and more severe symptoms.If one parent is a carrier (affected) (Hh/hh), offspring will have 50% risk of the defect.
Describe the concept of an X-linked recessive disease. Give two examples
X-linked recessive diseases are carried on the X chromosome. As such, they can only affect men (as they have only one X chromosome – no redundancy), and can only be carried by women (men are affected, for women, the other X is dominant over the recessive).Two examples are red/green colourblindness and Haemophilia A.
What is a sex-linked genetic disorder?
A sex-linked genetic disorder is one that is carried on either the X or Y chromosome. They are very easy to map through a family pedigree, which can then be useful for characterising the type of disease?
Describe the concept of an X-linked dominant disease.
An X-linked dominant disease is a disease caused by a dominant allele on the X chromosome. They can affect either men (only have one X) or women (diseased X is dominant). If the father is affected, only the daughters can get it (through X from him), whereas if the mother is affected, any child can get it (through X from her).
Explain the concept of co-dominant inheritance. Give an example.
Co-dominant inheritance is a situation when two different alleles are both dominant. The most obvious example is blood groups - Ao, Bo, AB, oo.
What is a complex genetic disorder?
Most genetic disorders are complex. They are caused by a combination of factors (such as environment and lifestyle) that tend to exacerbate a genetic predisposition to a particular disease. Thus they are MULTIFACTORIAL. IComplex disorders can also be POLYGENIC (must inherit more than one gene to present with symptoms). While there is an element of inheritance, they are not easily mapped like simple disorders - there is no obvious pattern. It is very difficult to identify the root
Is there a clear causal link with complex genetic disorders?
No. The disease mechanisms are not fully understood. You could have full genetic predisposition, and all lifestyle/environment risk factors, and never present with a symptom. Or, you could have just one genetic predisposition, with none of the lifestyle risk factors, and present as a severe case.
How is the heritability of complex genetic disorders studied?
Frequently through twins:CONCORDANCE exists if both twins develop the same trait. This then suggests there is a genetic link (such as with autism).DISCORDANCE exists if both twins don’t develop the same trait. This suggests there is not a genetic link (as with infectious diseases).
What is an inherited disorder?
A disease in which a faulty gene/s causes a change to normal phenotype or function. As they relate to faulty genes, they cause a much smaller change to the genome than chromosomal disorders. Thus, they are compatible with life, but can lead to significant disease.Inherited disorders have a pattern of inheritance in the family, thus can be easily mapped.
What is a simple inherited disorder?
Also called a Mendelian inherited disorder. Caused by either dominant or recessive ALLELES. They can be mapped and understood on Punnet Squares
