9/18 Genetic recesive diseases and X-linked

Question 1

what would type 1 collagen defects lead to?

Answer 1

bone fragility and multiple fractures, ostiogenesis imperfecta Type III

Question 2

what is a blueing of the eyes and what would it be associated with?

Answer 2

blue sclerae and this would be seen in osteogenesis imperfecta

Question 3

what is it called when the same mutation affects multiple tissues?

Answer 3

pliatropia

Question 4

what is it called when mutations at different loci can give rise to the same clinical disease

Answer 4

locas heterogeneity

Question 5

osteogenisis imperfecta is example of at least two important genetic principles?

Answer 5

locas heterogeneity; allelic heterogenitity (missense vs. nonsense gives different outcomes); pliatropia; variable expression; Often see germline mozaisism.

Question 6

what type of mutation would lead to mild OI?

Answer 6

major mutation

Question 7

what type of mutation leads to severe OI?

Answer 7

missesnse mutation.

Question 8

why do we have worse type of OI with mis-sense mutation?

Answer 8

we “poison” the good with the bad one or there is a dominant negative effect.

Question 9

what would suggest autosomal ressesive in a pedegree

Answer 9

neither of the parents are expressing the disease, there might be consiengwinity (mating of second cousin or closer), sibling also expresses the disease. (.25 chance)

Question 10

principles of recessive inheritence

Answer 10

disease phenotype typically in only one geerration; consaguinity; male and females affected in euqal; .25 chance

Question 11

features of CF

Answer 11

elevated sweat chloride; pancreatic insufficiency (.85); sterility in .98 of males due to bilateral vas deferen absence; pulmonary insufficiency

Question 12

what is typical of CF in the pancreaus

Answer 12

fat and fibrotic leasoions

Question 13

what leads to fibrosis of the pancreaus in CF patients/

Answer 13

ducts get plugged and enzymes build up and digest the pancreaus first

Question 14

what kills .9 of CF patients.

Answer 14

pulmonary failure

Question 15

what causes digital clubbing

Answer 15

hypoxia

Question 16

why would CF lead to digital clubbing?

Answer 16

CF leads to chronic hypoxia due to poor lung function.

Question 17

what does CFTR encode

Answer 17

chloride ion channel

Question 18

what if the CFTR is not working

Answer 18

Cl builds up in the cell in the lungs and Cl is not reabsorbed into the cells in sweat glands.

Question 19

why is CF an example of allelic heterogeneity?

Answer 19

there are lots of different alleles that can be mutated to cause the CF phenotype.

Question 20

what are some expamples of mutations of CF?

Answer 20

Class I - VI; Class I, II don’t make it to the membrane. Class III-VI are defective or turn-over too quick.

Question 21

what is the most common CF genotype

Answer 21

Class II where it doesn’t fold and gets proteoliyzed

Question 22

What is the conventional treatment for Cystic Fibrosis

Answer 22

Chest physical therapy; pancreatic enzyme replacement; antibiotics.

Question 23

what are some new treatments of Cystic Fibrosis?

Answer 23

DNAse; ribosomal read through of stop codons; Ivacaftor (open chloride channel);; Gene therapy??

Question 24

what is a modifyer loci mutation

Answer 24

mutation at a locus that is not the gene but still affects the function of the gene.

Question 25

what is Ivacaftor

Answer 25

a drug that opens the Cl channel for CF patients and helps to fix the phenotype.

Question 26

what are some other problems that are associated with CFTR mutations, (in non-CF patients)

Answer 26

congenital bilateral deferens; disseminated bronchiectasis; idiopathic pancreatitis; chronic sinusitis.;

Question 27

what is the karyotype of a male?

Answer 27

XY

Question 28

how is the XY chromosem different?

Answer 28

The X chromosome codes for alot, the Y is extremely small and codes for very little.

Question 29

why do females not have more differences than males with two Xs?

Answer 29

X inactivation in female embryos

Question 30

what is X inactivation?

Answer 30

one of the X-chromosomes is inactivated in early cell division in the envelopment of an embryo and one of the X is just a bar body

Question 31

why are all females somatically mosaic?

Answer 31

they have a mixture of female and male X chromosomes activated in their cells.

Question 32

what makes a calico cat calico

Answer 32

somatic mosaicism in the activity of the X chromosomes.

Question 33

why do those with extra or missing X chromosome have a different phenotype?

Answer 33

the X inactivation is incomplete: portions of X chromosomes remain active in both copies

Question 34

What are some important characteristics of X inactivation?

Answer 34

occurs early in development of normal female embryos;; random with regard to inactivation of paternal or maternal X chromosomes;; fixed: all descendants of cell have same chromosome inactivated;; incomplete: only some X genes inactivated;; Methylation occurs in inactivated regions;; inactivation imprint is erased during oogenesis.

Question 35

what encodes a long noncoding RNA that coats the x chromosome to make a bar body?

Answer 35

XIST

Question 36

what are some characteristics of X-linked recessive pedigree

Answer 36

only males are expressing the disease;; no male to male transmission;; skipped generations. (affected male > Carrier female > affected male)

Question 37

what would the prob. be for affected male-normal female mating for Recessive gene

Answer 37

Zero percent occurence, Females are all carriers, and the males are normal.

Question 38

what would the prob. be for normal male-carrier female mating

Answer 38

50% males will be affected. 50% of females will be carriers.

Question 39

what would the prob. be for affected male-carrier female mating

Answer 39

50% of males are affected. 50% of females are affected, and 50% of females are carriers.

Question 40

how could a female express X-linked recessive traits?

Answer 40

By having an affected father and carrier mother

Question 41

what is a manifesting heterozygote?

Answer 41

They are carrier females that express some of the disease traits.