Lec 59: Medical Genetics II: Modes of Inheritance of Single Gene Disorders Flashcards Preview

Fundamentals > Lec 59: Medical Genetics II: Modes of Inheritance of Single Gene Disorders > Flashcards

Flashcards in Lec 59: Medical Genetics II: Modes of Inheritance of Single Gene Disorders Deck (13):

Identify the standard symbols used in pedigrees and explain how pedigree analysis is used in determining mode of inheritance.

Pedigree analysis allows you to study an inherited trait in a group of related individuals to determine the pattern and characteristics of the trait, including its mode of inheritance, age of onset, and phenotypic variability


Describe the common features of Autosomal Recessive Inheritance

Only homozygotes are affected

Horizontal transmission

Similar amount of both males and females affected

Consanguinity is often present

If both parents are affected, all children should be affected

If one parent is affected, all children are carriers

If one parent is affected and one is a carrier, ½ are affected and ½ are carriers


Describe the common features of Autosomal Dominant Inheritance:

Vertical Transmission

More males affected than females

Affected individuals have affected parent, will have 50% of affected children

Unaffected family members will have no affected children


Describe the common features of X-linked recessive Inheritance

More males affected than females

No father to son transmission

Daughters of affected men are all carriers

Carrier females will have 50% affected sons

Affected females will have affected fathers AND affected or carrier mothers


Describe the common features of X-linked dominant inheritance

Vertical transmission

Females affected twice as often as males

Affected males transmit trait to all daughters but no sons

Affected females transmit trait to 50% of daughters and 50% of sons


Explain why some mutations are dominant and list examples.

1) Haploinsufficiency: half of the normal amount of protein is not enough.

Ex: familial hypercholesterolemia. The receptor needed to get cholesterol from blood to cells is mutated causing elevated levels of serum cholesterol.

2) Dominant negative effect: a mutant protein interferes with the function of a normal protein

Ex: Osteogenesis imperfecta

3) Gain of function: New or enhanced property of the protein

Ex: Achondroplasia, Huntington disease


What is Allelic Heterogeneity?

Many genes have more than one mutant allele. Allelic heterogeneity is caused by different mutations in the SAME gene

Different alleles may lead to clinically indistinguishable phenotypes, different severity and/or extent of symptoms, and different clinical presentations.


What is Locus Heterogeneity?

The same condition can be caused by mutations in different genes. Locus heterogeneity is caused by mutations in DIFFERENT genes.


What is Penetrance?

The likelihood that the disease allele will result in the disease


Describe Delayed Onset

An individual may pass the allele on to offspring but due of unrelated causes prior to showing the disease (ie a disease that presents later in life such as Huntington’s disease).


What is Germline Mosaicism?

Mutation in the germ stem cell that results in mutated gametes

Ex: A family with two children affected with a dominant disease without prior family history= likely mosaicism of the gonads (highly unlikely that two mutations will occur spontaneously in two siblings).


Describe Pleiotropy

Diverse effects of a single gene on several organs

Ex: Marfan syndrome- mutations in fibrillin gene leads to connective tissue weakness. Can affect cardiac, skeleton, and eyes differently in different affected individuals.


Describe Variable Expressivity

The degree of clinical manifestation of the SAME mutant allele in different individuals.

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