Diseases of Premature Aging

Question 1

Hutchinson-Gilford Progeria Syndrome vaused by

Answer 1

Mutations in Lamin A gene

Question 2

Lamin A function

Answer 2

Found in nuclear lamina and important for strucutral stability of the nucleus

Question 3

Most common progeria causing mutation

Answer 3

C to I in exon 11 of Lamin A gene destroys 5’ splice site and uses cryptic site…leads to short proteins

Question 4

What does mutated form of protein still contain, what is it called, and what does it cause?

Answer 4

Farnesyl group
Progerin
Nuclear mopho abnormalities, disorg of heterochromatin, defective DNA damage and genomic instability

Question 5

Farnesyl in normal vs. mutated lamin A

Answer 5

It is cut off once it reaches lamina normally, not cut off and piles up during progeria

Question 6

Drugs that combat progeria do what?

Answer 6

Block addition of farnesyl

Question 7

Oligonucleotide tx for progeria

Answer 7

Put cells into the oligonucleatude and it hybridizes the aberrant splice site in lamin A mRNA and prevents its use in the splicing reactions so it have to use regular splice site

Question 8

how to inhibit farnesylation of progerm

Answer 8

Inhibit product of farnesyl precursor (statins)

Or inhibit farnesyl transferase via farnesyl transferase inhibitors

Question 9

Weird progeria fact

Answer 9

Progerin is being produced even if cells don’t have progeria

Question 10

Werner syndrome mutation and inheritance

Answer 10

Auto recessive

Mutation in WRN

Question 11

Major symptoms of Werner syndrome

Answer 11

Growth retardation
Alopecia, skin scleorsis
Cataracts

Hoarse voice
Diabetes
Osteoporosis
Immune abnormalities

Question 12

WRN normal functions

Answer 12

DNA repair, replication, telomerase maintencnace

Question 13

Werner syndrome exhibits

Answer 13

Varibale expressivity

Question 14

Telomeres

Answer 14

TC rich on one strand and AC rich on the other

Question 15

Why are telomeres needeed

Answer 15

Because on laggin strands, DNA at chromosome end is not replicated

Question 16

Telomerase

Answer 16

Can lenghten telomeric repeats

RNA and portein component…segment of RNA is complementary to telomeresequence

Question 17

Once 3’ overhang telomeric sequence is lengthened,

Answer 17

Okazaki fragment can made using it as a template during replication of lagging strand near chromosome end

Question 18

DKC cause

Answer 18

Mutations in protein and RNA components of telomerase

Dyskeratosis congenita

Question 19

Other diseases from telomerase failure

Answer 19

Bone Marrow failure syndrome

Pulmonary fibrosis

Question 20

DKC most problematic cells

Answer 20

Skin…early onset of aging…those most dependnent on telomerase activity affected most

Question 21

Kids born to older fathers

Answer 21

Have longer telomeres…could have greater longevity…alsomore likely to have schizophrenia and autism