16 nontraditional inheritance

Question 1

How does dosage compensation account for the X chromosome?

Answer 1

In females there are twice as many X chromosome protein products meaning drugs may have to be adjusted to account for this

Question 2

What is the Lyon Hypothesis?

Answer 2

One X chromosome in each XX cell is inactivated

Question 3

What are the three traits of inactivation?

Answer 3

random, fixed and incomplete

Question 4

How does mosaicism related to X inactivation?

Answer 4

all normal females have cell populations that express one or another allele, thus mosaicism

Question 5

How does inactivation on the X chromosome work?

Answer 5

the XIST region produces an RNA that coats the inactivated region, also there is a high degree of methylation and histone deacetylation

Question 6

What are the three well known sex linked disorders?

Answer 6

Hemophilia A, Duchenne’s muscular dystrophy, red-green color blindness

Question 7

What type of pattern is similar to sex linked disorders for females?

Answer 7

Sex linked inheritance will resemble autosomal recessive inheritance for only females

Question 8

How will x linked genes affect males?

Answer 8

They will always express it due to only retaining one X chromosome

Question 9

What will the offspring result be in an affected male and normal female cross?

Answer 9

No affected offsprings will be the result

Question 10

What is the defect in hemophilia A?

Answer 10

Factor VIII leading to poor clotting

Question 11

What types of mutations are severe in hemophilia A and what are mild

Answer 11

Nonsense, deletions and inversions are severe while missions mutations are mild

Question 12

What is the hallmark of Duchenne’s Muscular Dystrophy?

Answer 12

Severe progressive muscular atrophy leading to cardiac/respiratory failure by mid 20s

Question 13

What is an early diagnostic indicator for DMD?

Answer 13

Creatine kinase release that is up to 20 times the normal limit

Question 14

Explain the characteristics of the DMD gene

Answer 14

Largest gene known, dystrophin protein binds F-actin and dystroglycan and holds the myocyte together, in DMD the dystrophin is usually completely absent, if dystrophin is only altered = milder symptoms and named Becker MD

Question 15

What genes result in red-green color blindness and the proposed mechanism?

Answer 15

Genes coding for opsins are mutated in which unequal crossing over is the proposed mechanism

Question 16

What are the 5 characteristics of X-linked Dominant inheritance

Answer 16

Much less common than recessive, heterozy females are less affected, females twice as likely to be affected, seen in every generation, males receive from mother while females from both

Question 17

What are the three X linked dominant disorders?

Answer 17

Hypophosphatemic rickets, incontinentia pigmenti, rett syndrome

Question 18

What are the traits of hypophosphatemic rickets?

Answer 18

Kidneys cant absorb phosphate, leads to abnormal ossification

Question 19

What are the traits of incontinentia pigmenti?

Answer 19

Abnormal pigmentation and teeth, neuro/ocular disorders, males are always stillborn

Question 20

What are the traits of rett syndrome?

Answer 20

Autism, ataxia, retardation and only some males survive

Question 21

What are the four traits of Y linked inheritance?

Answer 21

Aka holandric inheritance, always father-son, usually involve spermatogenesis, homologs are on X chromosomes but crossing over causes them to escape inactivation

Question 22

What are the four traits of mitochondrial inheritance?

Answer 22

Mutation rate is high, always maternal, separate ribosomes/tRNA, circular chromosome

Question 23

What is mitoheteroplasmy?

Answer 23

When mitochondria inside a cell has different chromosomes

Question 24

What are three mentioned mitochondrial disorders?

Answer 24

Leber hereditary optic neuropathy (LHON), Myoclonic epilepsy with ragged red fiber (MERRF), Mitochondrial encephalomyopathy and stroke-like episodes (MELAS)

Question 25

What are the characteristics of LHON?

Answer 25

missense mutation causes optic nerve death at around 30 yo

Question 26

What are the characteristics of MERRF

Answer 26

Single base change in tRNA causes epilepsy, dementia and myopathy, MUCH more heteroplasmic than LHON or MELAS

Question 27

What are the characteristics of MELAS?

Answer 27

Same as MERRF except also repeated stroke

Question 28

What is the most common inherited form of mental retardation?

Answer 28

Fragile X syndrome

Question 29

What is the most common form of mental retardation?

Answer 29

Down syndrome (more than fragile X but not inherited)

Question 30

What is the rates of inheritance and pattern for Fragile X?

Answer 30

1/4000 males, 1/8000 females and odd inheritance pattern called sherman paradox

Question 31

What is the sherman paradox?

Answer 31

Patterns with fragile X where normal “transmitting” males occur (ie. Carrier of x linked but not affected), sisters of NTM are less affected than graddaughters, Daughters of NTM are never affected

Question 32

How does fragile X transmit over generations?

Answer 32

FMR1 gene’s CGG sequence can be triplet expanded during female meiosis, 50-230 is carrier range, sons of NTM have same number of triplets as father

Question 33

Where is the FMR1 gene most expressed and pathological result?

Answer 33

Mostly in the brain where repeats are methylated which results in mRNA abruptly halted at past 230 triplets

Question 34

What is the fragile X phenotype?

Answer 34

Macroorchidism, long face, large ears, prominent jaw

Question 35

What are the two disorders associated with genomic imprinting?

Answer 35

Prader willi and angelman’s syndrome

Question 36

What is the mechanism behind disorders of genomic imprinting?

Answer 36

Imprinting causes methylation of one or part of an allele region meaning all the expression comes from one of the chromosomes. When there is a mutation on the side being transcripted, the second chromosome cannot cover

Question 37

What are the genotype and phenotype of prader-willi and angelmans syndromes?

Answer 37

Prader-willi= paternal deletion with maternal imprinting, angelman’s syndrome = maternal deletion with paternal imprinting