Intro to Med Genetics

Question 1

How can be medical genetics be divided up?

Answer 1

Two clinical fields (clinical genetics and genetic counseling); three lab sciences (cytogenetics, molecular genetics, and biochem genetics)

Question 2

What is a mutation? What do mutations allow for?

Answer 2

Permanent, heritable change in sequence of genomic DNA; can give rise to new alleles to allow for adaptation to environment

Question 3

What are examples of neutral, positive, and negative mutations?

Answer 3

Neutral: blue eyes
Positive: sickle cell trait in countries with malaria endemic
Negative: sickle cell disease; cancer

Question 4

What are patterns of inheritance?

Answer 4

Dominant vs. recessive

X-linked vs. autosomal

Question 5

What is inherited gene complement compared to acquired gene complement?

Answer 5

Inherited: mutations from one or both parents (constitutional genome)
Acquired: single mutation gives rise to cells via clonal propagation (potentially deleterious; later in life)

Question 6

To be diagnosed with something, what must an individual have?

Answer 6

Core group of cardinal characters associated with that disease (range of variability)

Question 7

Biochemical genetics deals with what?

Answer 7

Inborn errors of metabolism (diagnosis, treatment, research)

Question 8

What is an inborn error of metabolism?

Answer 8

Deals with a specific enzyme defect producing a metabolic block: 1. substrate accumulation 2. product deficiency
Almost always recessive

Question 9

How is tyrosine converted to melanin?

Answer 9

Tyrosine to pigment A through tyrosine oxidase; pigment A to melanin through “Enzyme X”

Question 10

How do you get a grey/brown cat? An albino cat?

Answer 10

Block at “Enzyme X;” block at tyrosine oxidase

Question 11

What are two types of albinism?

Answer 11

Complete (red eyes)

Partial (some organs/tissue have pigment, like blue eyes of cat or brown eyes of boy)

Question 12

What is deficiency of shared enzyme?

Answer 12

Enzyme might function in multiple different related or unrelated pathways

Question 13

What are general features of an inborn error of metabolism?

Answer 13

Mental retardation, poor growth, general metabolism issues, neurological problems

Question 14

What are three examples of hyperphenylalaninemia?

Answer 14

PKU, variant PKU, tetrahydrobiopterin metabolism defects

Question 15

What is PKU? How is it inherited?

Answer 15

Phe hydroxylase deficiency, allowing for buildup of phenylpyruvic acid which is detected in the urine
Autosomal recessive

Question 16

How can PKU be treated?

Answer 16

Diet modification for kids early in life and pregnant women, since Phe can cross placenta to fetus and damage it

Question 17

How is non-PKU hyperphenylalaninemia compared to PKU? What about variant PKU relative to those two?

Answer 17

Non-PKU: deficit in Phe hydroxylase, but less damaging and might not require special diet
Variant: between the other two; might require diet, but not as restrictive as full-on PKU

Question 18

If someone has a BH4 metabolism defect, how can it be treated?

Answer 18

For Phe hydroxylase, add BH4 to supplement orally

To make dopamine from tyrosine, and serotonin from tryptophan, L-dopa or OH-trp are needed

Question 19

What are 3 characteristics of lysosomal storage diseases?

Answer 19

1. Recessive
2. Macromolecules cannot be degraded in lysosomes as lysosomal hydrolytic enzymes are mutated
3. Progressive degeneration

Question 20

What can lead to GM2 gangliosidoses?

Answer 20

Mutations in three different genes that produce 3 proteins that function together (alpha, beta subunits and activator)

Question 21

What are characteristics of Tay Sachs?

Answer 21

Autosomal recessive, Ashkenazi Jews susceptible; hexosaminidase A defect; GM2 gangliosides can’t be degraded; cherry red spot in retina; can’t walk; die between 2 and 4

Question 22

What builds up in mucopolysaccharidoses? Why?

Answer 22

Mucopolysaccharides or GAGs (repeating chains of disaccharides)
Specific enzyme needed to cleave the monosaccharide absent/defective

Question 23

What are some characteristics of mucopolysaccharidoses?

Answer 23

Permanent; progressive; short, delay, skeletal abnormalities, joint stiffness, thickened skin, heart, liver, spleen damage

Question 24

What is a major CT disorder with respect to collagen?

Answer 24

Osteogenesis imperfecta

Question 25

What is OI due to? How is it inheritied? What are the major characters?

Answer 25

Mutations in type I collagen
Autosomal dominant
Brittle bones and skeletal deformities

Question 26

Which OI type is the worst?

Answer 26

OI II (perinatal lethal) > OI III > OI IV (mild-moderate bone deformity and fracturing)

Question 27

What is Ehler-Danlos syndrome due to?

Answer 27

Mutations in different collagen genes leading to post-translational mod errors of collagen

Question 28

For Ehler-Danlos, what are the subtype characteristics?

Answer 28

Skin fragility (scarring); joint hypermobility; skin hyperextensibility/elasticity

Question 29

What is Marfan syndrome attributed to?

Answer 29

Fibrillin gene mutations

Question 30

Where are defects in Marfan’s seen?

Answer 30

Myopia, lens dislocation, cataracts, glaucoma, retinal detachment; dilatation and dissection of aorta; lung problems; joint laxity, scoliosis, tall, thin, long thin fingers

Question 31

How can Ehler-Danlos syndrome be inherited?

Answer 31

Autosomal recessive, dominant; X-linked recessive