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57 Cards in this Set
- Front
- Back
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What shows up more often in inbred groups?
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RARE auto recessive diseases
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Which auto recessive disorders will have increased frequency in a certain population?
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Only those that were introduced by a founder that is a member of that particular population.
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What population is Ellis vanCreveld restricted to?
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Amish from Europe in Lancaster, PA
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What are the defects seen in Ellis vanCreveld?
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-Poly/syndactyly
-Dental defects -Heart defects -Foreshortened limbs |
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What is the gene locus for the Ellis vanCreveld disease? What is the gene product a critical factor for?
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On 4p - critical for chondrocytes during endochondral ossification.
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What is the Inbreeding coefficient for parent/child and siblings?
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1/4
-They share half their genes -1/2 x 1/2 = 1/4 -They are 1/4 identical |
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How much of their genes do first cousins, 3rd degree relatives, share? What is their ofspring's inbreeding coefficient?
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1/8 identical, so inbreeding coefficient for offspring is 1/16
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Why do we care about the inbreeding coefficient?
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Because consanguinity has a direct relationship with adverse pregnancy outcomes.
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What measurable quantity is affected by inbreeding? What nonmeasurable affects does it have?
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-IQ - 6 points for every 10% inbreeding coefficient.
-Morbidity and mortality |
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What patients will mainly be affected by an X-linked recessive gene defect? Why?
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Males - because they only have one X chromosome so nothing to cover it up.
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What is necessary for females to exhibit symptoms of an X-linked recessive gene defect?
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Homozygous alleles
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What will the genotypes of all daughters of an affected male with x-linked recessive gene be?
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Carriers (if he mated with a normal individual)
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If a female carrier mates with a normal male, what fraction of their sons will be affected?
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1/2
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What fraction of their daughters will be affected?
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none
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What fraction of their daughters will be carriers?
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1/2
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When females are affected by x-linked recessive gene defects, how does their condition to relate to the same in males?
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Less severely affected!
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Can affected males pass the gene on to their sons?
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No; they only pass on the Y gene to their sons.
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Can unaffected males transmit the disease? Are males ever carriers?
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no
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What do more severe phenotypes of x-linked recessive diseases indicate?
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That the disease is a new mutation, not passed on by a carrier.
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What is a factor that contributes to the development of a new mutant and heterozygous female?
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Age of the father
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What is the typical pedigree pattern of X-linked recessive diseases?
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Oblique
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What is a prototypical X-linked recessive disease?
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Mucopolysaccharidosis type II
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What is another name for Mucopolysaccharidosis type II?
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Hunter syndrome
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What is deficient in Hunter syndrome and what is the effect?
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-Iduronate 2 sulfatase deficient
-Buildup of GAGs |
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What are the physical abnormalities seen in Hunter syndrome?
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-Coarse facial features
-Large head -Hepatosplenomegaly -Thickened heart valves |
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What is the incidence of Hunter syndrome?
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1/600000
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And what is the chromosome that carriers the gene for I2s?
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X
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What complications develop in Hunter syndrome?
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-Enlarged liver/spleen
-CNS involvement -Hearing loss -Obstructive airway disease |
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What are some early signs of MPS II (hunter)?
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-Hernias
-Runny noses -Ear infections |
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What is a possible test that may tipoff the diagnosis of MPS II?
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Urine GAGs - dermatan sulfate and heparan sulfate
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What allows a definitive diagnosis of Hunter syndrome?
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Measurement of I2S activity
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How is prenatal diagnosis of MPS II done?
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By measuring I2S activity in amniotic fluid or chorionic villus tissue.
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What is the treatment for Hunter syndrome?
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Elaprase
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What is Elaprase?
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Synthetic I2S
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What is the hallmark feature of Prader Willi syndrome?
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Complete loss of control of appetite at age 3 or so
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What are Prader willi syndrome babies like at birth?
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hypotonic - floppy
poor feeding - undernourished |
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What is the major health risk to Prader Willi syndrome kids as they age?
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They become obese if access to food is not controlled.
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What is the genetic abnormality in Prader willi syndrome patients?
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Loss of a piece of Ch' 15
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How is Prader Willi syndrome confirmed?
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With a flourescent probe
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What is the hallmark of Angelman syndrome?
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Severe mental retardation
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What is the gene defect in Angelman syndrome? (75%)
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Same region of Ch' 15 is deleted as in Prader Willi!
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Is there any phenotypical identity between Angelman and Prader Willi patients?
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no
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What is the non PC term for Angelman's patients?
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Happy Puppets
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What is the factor that determines whether a Ch' 15 deletion is Prader Willi or Angelman?
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Whether the deletion is on a maternal or paternal chromosome.
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Which chromosome is deleted in Prader Willi syndrome?
Which chromosome is deleted in Angelman syndrome? |
Prader Willi = Paternal
Angelman = Maternal |
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Chromosome deletions are only seen in about 70% of Prader willi and Angelman syndrome patients; what about the others?
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They inherit 2 copies of the other parent's chromosome
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What do Angelman patients with no gene deletion inherit?
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2 Paternal chromosome 15's - so they're still massing the maternal
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What do Prader Willi patients with no gene deletion inherit?
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2 maternal chromosome 15's - so they're still missing the paternal
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What is it called when 2 chromosomes are inherited from the same parent?
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Uniparental disomy
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So the 2 etiologies for Angelman and Prader Willi syndromes are:
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-Deletion
-Uniparental disomy |
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What Ch 15 gene is abnormal in
-Prader willi -Angelman |
Prader willi = SNRPN
Angelman = UBE3A |
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What is needed for normal SNRPN?
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Maternal inactivation, and paternal activation so that offspring get ONE ACTIVE COPY
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So the result of deleting the paternal gene or inheriting 2 maternal copies of SNRPN is:
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Prader Willi syndrome - no active copy of SNRPN
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What is needed for normal UBE3A expression in offspring?
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-One inactive paternal copy
-One active maternal copy |
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So the result of maternal deletion of 2 paternal inheritances of UBE3A is:
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Angelman syndrome - no active copy of UBE3A at all
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What is the inactivation process called?
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Imprinting
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How is imprinting done?
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By methylation of cytosine residues on DNA
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