Human genetics

Question 1

What is the inheritance pattern of cystic fibrosis?

Answer 1

Single-gene, autosomal recessive, with over 2000 mutations (leading to varying levels of severity).

Question 2

What are compound heterozygous?

Answer 2

Individuals that possess two different mutated alleles

Question 3

What is the inheritance pattern for PKU?

Answer 3

Phenylketonuria (PKU) is another example of an autosomal recessive disorder with almost 400 known mutations in the gene.

Question 4

When is a gene considered polymorphic?

Answer 4

When two or more phenotypes for a given gene clearly exist within a population.

Question 5

What mutations are generally considered autosomal dominant unless proven otherwise?

Answer 5

Mutations in structural genes

Question 6

Inheritance of autosomal dominant traits:

Pedigree analysis

Answer 6

• a vertical pattern of inheritance, meaning the disease trait does not skip generations
• the trait appears equally in either sex
• the trait appears in roughly half of all children
• there is father-to-son transmission of the trait – important in distinguishing autosomal dominant inheritance from sex-linked inheritance

Question 7

What does “genetically lethal” mean?

Answer 7

Unable to produce offspring

Question 8

What type of mutation can give rise to an autosomal dominant trait without a family Hx of the trait?

Answer 8

Germline mutations and mosaicism may also account for the appearance of autosomal dominant conditions when there is no relevant family history.

Question 9

What inheritance pattern is generally thought to produce a phenotype expressing metabolic dysfunction?

Answer 9

Autosomal recessive disorders

Question 10

What disease is well known for age-dependent penetrance?

Answer 10

Huntington’s disease (autosomal dominant)

Question 11

What is NF1?

Answer 11

Neurofibromatosis (NF type 1): is an autosomal dominant disease with complete penetrance but that shows variable expression. The gene, NF1 codes for neurofibromin, a tumor suppressor.

Question 12

What is pleiotropy?

Answer 12

In pleiotropy, gene mutations exert effects on multiple organ systems. … Marfan syndrome is an autosomal dominant condition; a mutation in the fibrillin gene (located on 15q21.1) results in unusually stretchable connective
tissue. Connective tissue is part of all organs; in Marfan syndrome the ocular, skeletal and cardiovascular systems are most severely affected.

Question 13

What is locus heterogeneity?

Answer 13

A single disease phenotype that is caused by mutations at different loci (genes on different chromosomes). For example, adult polycystic kidney disease presents with a progressive accumulation of renal cysts. Cysts may also be seen in the liver; in addition to cysts, hypertension, cerebral aneurysms and cardiac valve defects are common. Most forms of human polycystic kidney disease are autosomal dominant conditions due to mutations in the PKD1 gene located on chromosome 16 or the PKD2 gene located on** chromosome 4**

Question 14

List examples of X-linked dominant disorders:

Answer 14

There are fewer X-linked dominant disorders compared to X- linked recessive disorders, and these are often lethal in males. Some common X-dominant
diseases include Fragile X syndrome , Rett syndrome and Incontinentia Pigmenti.

Question 15

What are the characteristics of mitchondrial inheritance?

Answer 15

While males show mitochondrial disorders, inheritance is exclusively through females.

Question 16

List examples of nucleotide repeat expansion:

Answer 16

nucleotide-repeat expansions are known to cause to several dozen human diseases.

• Huntington disease – an autosomal dominant condition causes loss of motor control, dementia, and affective disorder. It is caused by a CAG trinucleotide repeat. Repeats of 6 – 34 CAG sequences are normal; repeats of between 36 - 121 sequences signify disease. Huntington disease onsets later in life; it shows age-dependent penetrance.

* Friedreich ataxia – an autosomal recessive condition results in random limb movements, speech disorders (due to motor function impairment or dysarthria), cardiomyopathy, and weakness in the legs. Friedreich ataxia is caused by an increase in **GAA repeats **(6 – 32
is normal), from 200 – 1700 repeats are seen in disease conditions.

• Fragile X syndrome – an** X-linked dominant** condition leads to intellectual impairment, abnormal facial features, and macroorchidism in surviving males. It is causes by an increase in a CGG repeat (4 – 39 is normal) to from 200 – 900 in disease conditions.

* Myotonic dystrophy, an autosomal dominant disorder that is the result of a CTG nucleotide- repeat expansion. This phenomenon of earlier onset from one generation to the next is known as anticipation