Human Diseases: Genetic Cause and Basics

Question 1

What gene is responsible for Sickle Cell Disease and what goes wrong?

Answer 1

Missense mutation in HBB gene–> Incopration of different amino acid into the B-Globin protein.

Question 2

What gene is responsible for Hemophilia B and what goes wrong?

Answer 2

Point mutation in UTR of F9 gene–> Deficiency of Factor IX protein.

Question 3

What gene is responsible for Neurofibromatosis Type I (NF1) and what goes wrong?

Answer 3

Nonsense mutation introduces stop codon into NF1 coding region–> Shortened neurofibronin protein is unstable.

Question 4

What gene is responsible for Tay Sachs disease and what goes wrong?

Answer 4

4 Base Insertion and subsequent Sice Site mutation in HEXA gene–> deficiency in lysosomal hexoaminidase protein.

Question 5

What gene is responsible for a-thalassemia and what goes wrong?

Answer 5

Large deletion often due to aberrant recombination between a-globin genes

Question 6

What is responsible for Menke’s disease and what goes wrong? Inheritance mode?

Answer 6

X linked inheritance.

Copper deficiency–> lysyl oxidase can’t make protein–> Flacid.

Question 7

What is responsible for OI and what goes wrong? Inheritance mode?

Answer 7

Autosomal Dominant inheritance.
Collagen defects in type I collagen.
Sx include retarded wound healing, twisted spine, blue sclera, bone fractures, etc.
Hallmarks of types 1-4.

Question 8

Ehlers-Danlos Sndrome

Answer 8

Heterogeneous inheritance.

Caused by defects in metabolism of fibrillar collagen-> fragile, stretchy skin.

Question 9

Emphysema

Answer 9

alpha 1 antitrypsin deficiency

elastase allowed to degrade elastin–> alveolar walls destroyed.

Question 10

Marfan Syndreom

Answer 10

Caused by defective FBN1 gene.

Impaired structural integrity of skeleton, blue sclera, CV issues. Long fingers, pectus excavacum, enlarged aorta.

Question 11

Hurler Syndrome

Answer 11

Caused by α-L-iduronidase deficiency
Failure to degrade glycosaminoglycans–> presents with corneal clouding, developmental disability, dwarfing, dysmorphic facial features, upper airway obstruction, and hearing loss. Deposition in coronary artery leads to ischemia and early death

Question 12

Hunter’s Syndrome

Answer 12

an X-linked deficiency that presents with physical deformity and developmental disability. Caused by iduronate sulfatase deficiency (taking off a sulfate). Treated with enzyme replacement therapy

Question 13

Xeroderma Pigmentosum

Answer 13

Mutation in XP proteins or ERCC1. Unable to repair UV damage via NT excision repair–> mutations and skin cancer prevalent.

Question 14

Lynch Syndrome

Answer 14

Mutations in genes involved in mismatch repair. (MLH1 or MSH2 most common. Autosomal dominant. Major phenotype is colorectal cancer.

Question 15

Classic Galactosemia

Answer 15

Caused by Galactose-I-phosphate uridydyltransferase deficiency which leads to lactose intolerance. (can’t have breakst milk, no lactose or galactose).

Question 16

Galactokinase deficiency

Answer 16

build upf of open and closed forms of Galactose. Open forms leads to cataracts.

Question 17

Galctose epimerase deficiency

Answer 17

UDP-Glucose-4-epimerase

Question 18

Diarrhea

Answer 18

defect in disaccharide activity causes lack of absorption which leads to increased osmotic pressure due to extra particles–> water flows out.

Question 19

Congenital sucrase-isomaltase deficiency (CSID)

Answer 19

SI complex is single polypepdite–> malfunction leads to decreased digestion of both sucrose and isomaltose–> malnutrition