Thursday Lecture 1

Question 1

Epidermolysis Bullosa Simplex

Answer 1

autosomal dominant
(CT disease causing blistering with minor injury/rubbing of the skin)

Question 2

Junctional Epidermolysis Bullosa

Answer 2

autosomal recessive
(disease affecting laminin and collagen; also causes blistering with rubbing)
*do see some pleiotropy (multiple effects from mutation in one gene)

Question 3

Dystrophic EB

Answer 3

autosomal recessive or dominant
(defects in collagen VII)
*having too short a collagen here is less disruptive than having a wrongly shaped.structured collagen

Question 4

Sickle Cell Disease

Answer 4

• behaves as autosomal recessive
• can’t differentiate between AA and AS genotypes
• skips generates - affected individuals have normal parents
• can express codominance (when both alleles expressed)
• when under reduced oxygen tension, sickle-cell trait is behaving as an autosomal dominant (AS and SS genotypes can’t be differentiated)

Question 5

Locus heterogeneity vs Allelic heterogeneity

Answer 5

Locus heterogeneity
- single phenotype or disorder can be mapped to any one of multiple different loci (genes)

Allelic heterogeneity
- different mutations of same gene can cause same mutation/phenotype

Question 6

General mechanistic trends:

autosomal dominant

Answer 6

Structural Proteins:

• dominant negative:
• –> collagenopathies
• –> fibrillinopathies

DNA Repair Proteins:
- cancer syndromes

Signaling Molecules:
- neurofibromatosis & phagomatoses

Question 7

General mechanistic trends:

autosomal recessive

Answer 7

Enzymes

• inborn errors of metabolism
• albinism

Ion channels
- Cystic fibrosis

Hemoglobins
- hemoglobinopathies

Question 8

Non-random mating

Answer 8

• assortative mating
• consanguinity
• inbreeding

ex: can cause albinism

Question 9

Albinism

Answer 9

caused by lack of pigmentation, can be in varying degrees

• typically think of it as autosomal recessive disorder
• but get rest of story, there might be consanguinity etc.
• albinism actually has a horizontal inheritance pattern, characteristic of true autosomal recessives
• the expression appears to skip generations??

Question 10

Phenylketonuria

Answer 10

• inborn error of metabolism
• in that specific pedigree, why is PKU so frequent in generation V (was not seen in any other generation)?
• –> consanguinity, geographic isolation

Question 11

geographic isolation

Answer 11

can result in more frequent mutation

Question 12

X-linked icthyosis vulgaris

Answer 12

• increased cholesterol sulfate, decreased cholesterol in stratum corneum
• decreased skin shedding - flaking
• abnormal quad screen and delayed partuition (birth) by carrier mothers

Question 13

inbreeding

Answer 13

• occurs when both members of a reproducing couple have a common ancestor
• inbreeding increases the chances of a rare recessive allele appearing in the homozygous condition
• inbreeding can be expected in:
• – geographically isolated demes
• – socially isolated demes
• – ex: amish, ashkenazi jews, acadians, some american indian tribes, remote island populations

Question 14

multi-factorial inheritance

Answer 14

• inheritance involving many factors
• involves any combination of more than one gene set (i.e., more than one locus)
• the gene sets contribute equally or unequally (epistasis - interaction between genes that are not alleles)
• a major environmental component may also exist

Question 15

General sequence to think through when looking at pedigrees

Answer 15

• are there multiple single generation(s) affected? (dominant or recessive)
• gender bias? significantly more males than females?
• both genders transmitting disease or just one?
• x-linked? no male-male transmission; if there is, stick to autosomals
• is there a reason why this family would not be behaving typically? any recessive disorders I have not otherwise recognized?