16 nontraditional inheritance Flashcards
How does dosage compensation account for the X chromosome?
In females there are twice as many X chromosome protein products meaning drugs may have to be adjusted to account for this
What is the Lyon Hypothesis?
One X chromosome in each XX cell is inactivated
What are the three traits of inactivation?
random, fixed and incomplete
How does mosaicism related to X inactivation?
all normal females have cell populations that express one or another allele, thus mosaicism
How does inactivation on the X chromosome work?
the XIST region produces an RNA that coats the inactivated region, also there is a high degree of methylation and histone deacetylation
What are the three well known sex linked disorders?
Hemophilia A, Duchenne’s muscular dystrophy, red-green color blindness
What type of pattern is similar to sex linked disorders for females?
Sex linked inheritance will resemble autosomal recessive inheritance for only females
How will x linked genes affect males?
They will always express it due to only retaining one X chromosome
What will the offspring result be in an affected male and normal female cross?
No affected offsprings will be the result
What is the defect in hemophilia A?
Factor VIII leading to poor clotting
What types of mutations are severe in hemophilia A and what are mild
Nonsense, deletions and inversions are severe while missions mutations are mild
What is the hallmark of Duchenne’s Muscular Dystrophy?
Severe progressive muscular atrophy leading to cardiac/respiratory failure by mid 20s
What is an early diagnostic indicator for DMD?
Creatine kinase release that is up to 20 times the normal limit
Explain the characteristics of the DMD gene
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
What genes result in red-green color blindness and the proposed mechanism?
Genes coding for opsins are mutated in which unequal crossing over is the proposed mechanism
What are the 5 characteristics of X-linked Dominant inheritance
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
What are the three X linked dominant disorders?
Hypophosphatemic rickets, incontinentia pigmenti, rett syndrome
What are the traits of hypophosphatemic rickets?
Kidneys cant absorb phosphate, leads to abnormal ossification
What are the traits of incontinentia pigmenti?
Abnormal pigmentation and teeth, neuro/ocular disorders, males are always stillborn
What are the traits of rett syndrome?
Autism, ataxia, retardation and only some males survive
What are the four traits of Y linked inheritance?
Aka holandric inheritance, always father-son, usually involve spermatogenesis, homologs are on X chromosomes but crossing over causes them to escape inactivation
What are the four traits of mitochondrial inheritance?
Mutation rate is high, always maternal, separate ribosomes/tRNA, circular chromosome
What is mitoheteroplasmy?
When mitochondria inside a cell has different chromosomes
What are three mentioned mitochondrial disorders?
Leber hereditary optic neuropathy (LHON), Myoclonic epilepsy with ragged red fiber (MERRF), Mitochondrial encephalomyopathy and stroke-like episodes (MELAS)
What are the characteristics of LHON?
missense mutation causes optic nerve death at around 30 yo
What are the characteristics of MERRF
Single base change in tRNA causes epilepsy, dementia and myopathy, MUCH more heteroplasmic than LHON or MELAS
What are the characteristics of MELAS?
Same as MERRF except also repeated stroke
What is the most common inherited form of mental retardation?
Fragile X syndrome
What is the most common form of mental retardation?
Down syndrome (more than fragile X but not inherited)
What is the rates of inheritance and pattern for Fragile X?
1/4000 males, 1/8000 females and odd inheritance pattern called sherman paradox
What is the sherman paradox?
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
How does fragile X transmit over generations?
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
Where is the FMR1 gene most expressed and pathological result?
Mostly in the brain where repeats are methylated which results in mRNA abruptly halted at past 230 triplets
What is the fragile X phenotype?
Macroorchidism, long face, large ears, prominent jaw
What are the two disorders associated with genomic imprinting?
Prader willi and angelman’s syndrome
What is the mechanism behind disorders of genomic imprinting?
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
What are the genotype and phenotype of prader-willi and angelmans syndromes?
Prader-willi= paternal deletion with maternal imprinting, angelman’s syndrome = maternal deletion with paternal imprinting
