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197 Cards in this Set
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hardy weinberg equation
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p^2 + 2pq + q^2 = 1
p + q = 1 p^2 is the autosomal dominant 2pq is the heterozygous q^2 is the homozygouse recessive |
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disease alleles, q are much less common than normal alleles, p. Therefore p is approximately equal to 1. THen the freq of Aa is?
Frequenccy of aa is? |
2q
q^2 |
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autosomal recessive
-the disease frequency is equal to? -the carrier frequency is? |
dz freq = q^2
carrier freq = 2q |
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autosomal dominant
-the disease frequency is approx equal to? |
the carrier freq = 2q
* homozygotes are rare |
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X-linked recessive
-the affected male freq is? -the carrier freq is? |
affected male freq = q
carrier freq = 2q |
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X-linked dominant
-the affected male freq is? -the affected female freq is? |
affected male freq = q
affected female freq = 2q |
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list autosomal dominant diseases
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familial hypercholesterolemia
*not 100% penetrant postaxial polydactyly Neurofibromatosis adult polycystic kidney disease Huntington's disease Marphan's syndrome osteogenesis imperfecta Neurofibromatosis Retinoblastoma PHARM FON |
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list autosomal recessive diseases
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tyrosinase negative albinism (OCA-1)
cystic fibrosis PKU (autosomal recessive inborn error of metabolism) diastrophic dwarfism medium chain acyl-coenzyme A dehydrogenase deficiency (MCAD) congenital deafness |
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list X-linked recessive diseases
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Hemophilia
Glucose-6 phosphate dehydrogenase deficiency Duchenne Muscular dysrophy (and becker MD) |
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recurrence risk for someone with an autosomal dominant disease is?
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50%
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if someone has an autosomal dominant affected disease their genotype is? (unless otherwise indicated)
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Aa
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in autosomal dominant disease problems, assume unaffected is what genotype? (unless otherwise indicated)
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aa
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what autosomal dominant dz is 100% penetrant, w/ no delayed age of onset?
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postaxial polydactyly
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If the freq of familial hypercholesterolemia is 1/500 what is the approximate frequency of heterzygotes?
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1/500
AutoDom dz so freq of dz is freq of heterozygotes |
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if you see a pedigree with horizontal pattern of inheritance, dz phenotype seen in multiple siblings, but usually no earlier generations affected, sex ratio equal what interference pattern should you suspect?
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autosomal recessive
*consanguinity is sometimes seen, most cases appear sporadic |
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in autoreces dz, what will the offspring of an affected individual be?
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all carriers
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what is the usually recurrence risk for autosomal recessive diseases?
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25%
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CF occurs in 1/2500 people in the Northern Eurpean Caucasian population. What is the carrier frequency.
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CF is autorecessive so, 1/2500 = q^2 (the disease freq)
so q=1/50 so carrier freq is 2q = 1/25 |
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explain the 2/3 rule in autosomal recessive inheritance patterns.
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if no children are affected, you assume only one of the parents is a carrier, so the probability that one of their children will be a carrier is 1/2; however, if one of the children is affected, you know both parents must be carriers. Then the probability that one of their UNAFFECTED kids will be a carrier is 2/3.
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consanguineous mating risk of:
1st degree relative 2nd degree relative 3rd degree relative 4th degree relative |
1. 30%
2. 15% 3. 7% 4. 3% |
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if you do not know the carrier status of unaffected, unrelated spouse of a homozygous affected individual (dealing with an autsomal recessive gene), waht is the probability of an affected child?
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1/2 x carrier frequency (2q)
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CF is caused by?
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mutations to the CF transmembrane Regulator gene (CFTR gene)
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what is the probability that two carriers of CF will have none of 3 children with CF?
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3/4 x 3/4 x 3/4
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what is the probability that two carriers of DF will have 1 of 3 children with CF?
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1/4 x 3/4 x 3/4 + 3/4 x 1/4 x 3/4 + 3/4 x 3/4 x 1/4
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tay-sachs dz is a recessive degen neurologic disorder. The freq of Tay-seachs carriers among ashenzi jes is 1/30. The freq of Tay-sachs carriers among Caucasias is 1/300. what is the chance that a child of each union will have Tay Sachs?
1. both parents ashkenazi jews 2. mother has an affect child by a previous union, the fater is an ashenize jew 3. mother is an ashkenazi, the father is caucausian |
1. 1/30 (carrier chance) x 1/2 (chance to pass it down) x 1/30 x 1/2 (other parent is the same chance)
2. mother is obligate carrier 1/2 x 1/30 x 1/2 3. 1/30 x 1/2 x 1/300 x 1/2 |
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a man whose brother has cystic fibrosis wants to know his risk of having an affected child; the prevalence of cystic fibrosis is 1 in 1600 individuals
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brother has 2/3 chance of being a carrier (both of his parents are obligate carriers b/c brother has dz)
b/c 1/1600 = q^2, the chance his wife is a carrier too is 2q or 1/20. So the chance that they have an affected child is 1/20 x 2/3 x 1/4 = 1/120 |
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an african-american couple with a normal family history wants to know their chance of having a shild with sickle cell anemia; the incidence of sickle cell trait is 1 in 8 for african americans.
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incidence of sickle cell trait is equal to the number of carriers so.
1/8 x 1/8 x 1/4 (chance of of homozygous recesive) = 1/256 |
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a woman who married her first cousin wants to know the risk of having a child with cystic fibrosis b/c her grandmother died of cystic fibrosis
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b/c grandmother is homozygous recessive both husband and wife's parents would have one parent obligate carriers. So each would have a 1/2 chance of getting the trait and becoming a carrier and then a 1/4 chance to make a homozygous recessive baby
(1/2 x 1/2 x 1/4 = 1/16) |
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what IEM is this:
hypoglycemia, acidosis, elevated urine dicarboxlic acids (worsens with fasting to cause carnitine depletion) |
disorder of fatty aid oxidation
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what IEM is this:
alkalosis, elvated serum ammonia |
urea cycle disorder
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what IEM is this:
hypoglycemia, acidosis, elevated serum leucine, isoleucine, and valine |
maple syrup disease (MSD)
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what IEM is this:
hypoglycemia, acidosis, elevated urine reducing substances, liver failure |
galactosemia
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what IEM is this:
hepatomegaly (liver failure(, elevated liver enz, and elvated tyrosine, elevated serum leucine, isoleucine, and valine |
tyrosinemia
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what is abnormal allele frequency of 1/100 referring to?
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q=1/100
so, carrier freq=2q=1/50 |
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a 2-year-old child presents with dark urine. Her parents are 1st cousins. Assuing that this is a genetic disease with an abnormal allele (a) frequency of 1/100, what is the risk of unaffected sibing of proband to transmit the disease with an unrelated spouse?
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allele freq is 1/100, so carrier freq is 1/50 (2q)
probability that sibling is carrier is 2/3, and probability that this match will have an affect kid is 1/4. 1/50 x 2/3 x 1/4 = 1/300 |
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folate deficiency in the periconceptional period has been assoiciated with?
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neural tube defects (NOT MENTAL RETARDATION)
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who are obligate carriers in an x-linked recessive pattern?
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mothers of affected sons, all daughters of affected sons
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what protein is affected in hemophilia A?
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defect in factor VIII
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what protein is affected in hemophilia B?
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defect in factor IX
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name the dz; common in mediterranean and African, an acute self-limiting anemia secondary to intravascular breakdown of RBCs due to oxidative damage to RBC due to decreased stability of glucose-6-phosphate dehyrdogenase
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G6PD def x-linked recessive
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if a woman has a 1/2 chance to be a carrier of an x-linked disorder, and she has 3 unaffected sons, what is her recurrence risk of having an affected son?
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1/9 using bayesicounseling
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autosomal dominant condition, you have two heterzygote parents, what is the chance that at lease one child of four inherited the dz?
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chance that no child did. 1/4 x 1/4 x 1/4 x 1/4 = 1/16
so probabily that at least one did is 1-1/16 = 15/16 |
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how do you explain an albino couple that has a normal child when albinism is autsomal recessive?
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locus heterogeneity
they both have albinism mutations at two different loci |
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describe the two types of genetic hetergeneity?
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allelic heterogeneity is where there are different mutations at the same locus which result in similar disease
locus heterogeneity refers to different mutations at different locus that result in similar phenotypes |
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what is pleiotropy?
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when there is multiple phenotypic body system effects from a single gene
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symptoms observed after treatment with certian drugs (anti-malarials or antibiotics), or after other stresses (infetion) is under the field called?
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pharmacogenetics
G6PD def having an attack after antimalrials and antibiotics |
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What id duchenne muscular dystrophy and what protein is affected?
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progressive muscle weakness in early childhood in affected boys, cardiomyopathy before age 20, life expectancy less than 30 years due to defects in the DMD gene which encodes for dystrophin protein
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how does becker muscular dystrophy relate to duchenne muscular dystrophy?
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it is allelic heterogeneity b/c it's a related dz in the the same gene, except milder
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in DMD, approx ________ of cases are due to new mutations, if only one affected individual , this could represent a spontaneous new mutation
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1/3
|
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In DMD, describe how a heterozygous female could be affected?
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x/autosome balanced translocation with a breakpoint in the DMD gene causing the mutation
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what is the sex ratio in x-linked dominant transmission?
what are some of the other features of the pedigree? |
twice as many females b/c they have twice the chance to get an X
vertical transmission, multiple, unskipped generations, no male to male transmission, dz in females often less severe than in males |
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when random x-inactivation occurs a implantation when there are about 100 cells in the embryo, what type of mosaicism is this?
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somatic cell mosaicism
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what is lyonization
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one x chromosome in each somatic cell in femals is inactivated randomlyh
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x chromosome is inactivated by DNA methylation, _____ RNA, and DNA condensation, in which the the inactivated X chromosome turns into a _________.
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XIST RNA
Barr Body |
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describe two situations when there is non-random x-inactivation
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when there is a balance translocation b/w an autosome and an X, the normal X is preferrentially inactivated to preserve the correct number of genes, secondly if there is a structuraly abnormalitiy such as a deletion, that X is preferentially inactivated
***in both these cases there is no mosaisim so if the saved X chromosome has a dz, the female is affected |
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what are 3 disease that display allelic heterogeneity?
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CF
familial Isolated Growth Hormone Deficiency Osteogenesis Imperfecta |
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there are both dominant and recessive forms of familial isolated Growth Hormone Deficiency. What is the difference in the mutations?
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recessive - mutations lead to reduced expression of GH
dominant - mutations lead to altered GH protein |
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describe the difference between OI type I and type II
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both autosomal dominant inheritance, mutation in the COL1A1 gene on chromosome 17
type I is less serve and involves 50% of normal collagen formed type II is more severe and forms abnormal collagen complexes with normal proteins resulting in less than half the normal protein level |
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what are 3 examples of locus heterogeneity?
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hemophilia A/B (X-linked recessive)
congenital deafness (autorecessive) dwarfism *also albinism |
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name the two types of dwarfism and the 2 types of inheritance
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achondroplasia - autosomal dominant
diastrophic - autosomal recessive |
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how is non-penetrance describe quantitatively from population data?
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the proportion of obligate heterozygotes taht express the gene phenotypically
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what is the classic example for non-penetrance?
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retinoblastoma (2 hit hypothesis)
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what are two examples of diseases with variable expressivity?
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neurofibromatosis
marphan syndrome |
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Marphan Syndrome affects skeletal muscle, eye and heart. All affected individuals in one family have the identical mutation in the ________ gene
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fibrillin gene
|
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name this dz:
most (2/3) have only mild cutaneous involvment. Sx include cafe-au-lait spots, lisch nodules and a few neurofibromas (non-malinant) |
neurofibromatosis
|
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what 2 inheritance patterns show a large portion of spontaneous new mutations and why?
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autosomal dominant and x-linked disorders b/c they have a very deleterious effect on reproductive fitness
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in what dz, are all occurrences due to new mutations?
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osteogenesis imperfecta type II
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when would you suspect germline mosaicism?
what types of diseases display this? |
when unaffected individuals have multiple children with the disease
autosomal dominant and X-linked (NF-1, OI, 10-20% of DMD and hemophilia) |
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what is proportion of spontaneous DMD mutations?
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1/3
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What is the classic case study disease for delayed age of onset?
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Huntington Disease
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name as many clinical signs as you can for IEM
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acute catastrophic illness after a period of normal behavior and feeding, seizures, jaudice, hepatomegaly, lethargy or oma, unexplained hemorrhage, recurrent vomiting, failure to thrive, apnea or tachypnea, FHx of neonatal deaths, parental consanguinity, sepsis, developmental delay, muscular hyptonia w/o known etiology, cardiomyopathy, eye abnormality, coarse facial features, unusual body odor
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what 3 types of lab test can you do to make a dx?
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blood/urine tests
second level metabolic screening (gass chromatography-mass spec) diagnostic confirmation using teriary biochemical or molecular genetic testing |
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name the dz:
defect in FA metabolism, recurrent reye syndrome-like (vomiting, rash, dehydration, hypoglycemia), autosomal recessive one chromosome 1p13. A985G mut in 90%. Build up a carnitine |
medium chain acyl-CoA Dehydrogenase Def
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clinical manifestations of IEM presenting neonatally
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comatose, rigid, extensor posturing, opisthotonus, recurrent generalized seizures, mild hypoglycemia, metabolic acidosis, ketosis
|
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when are neonatal screenings done?
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at 24-48 hours then 10-14 d
preterm imeadiately then 24-48, then 10-14 days |
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what did the learning curve issues bring up about neonatal screening?
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some diseases you find on the second screen (CPT I)
sensitivity is <100% LCHAD def some disorders are bening fatalities are not always preventable |
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what dz has this classic presentation?
hypoketotic hyperpoglycemia, liver dysfunction, cardiomyopathy |
CPT-1
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what is different about the Canadian/Alaskan varient of CPT-1
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decreased sensitivity to malonyl-CoA regulation, fever, infection, dehydration
*P479L variant *not in Hardy Weinberg Equilibrium *GC/MS not a good screen |
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T or F
In Maternal PKU, teratogenic risk is much higher than genetic risk |
True
|
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disorders detected on repeat screen
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hypothyroidism, CAH, galatosemia, homocystinuria, CPT-I
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in Bechkwith-Weidemann Syndrome a loss of methylation at DMR2 will only cause problems if?
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inherited from the mother, since paternal copic is not normally methylated
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in beckwith-widemann syndrome a mutation in the CDKN1C is only a problem if?
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inherited from the mother
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how can uniparental disomy lead to beckwith-widemann syndrome?
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if paternal UPD 11 you get the dz b/c you get two copies of IGF-2 and no CDKN1C
*maternal disomy (two CDKN1C) is not compatible with life |
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in PWS and AS, 70% are due to?
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same microdeletion affecting three gene (2 PWS and 1 AS)
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PWS gene area is made up of 5 genes and located on the paternally imprinted geneome, if theses get deleted you get?
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PWS
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AS gene area is a UBE3A that is active only on the maternally imprinted genome, if this area is deleted, you get?
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AS
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how does UPD lead to PWS?
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two maternal copies of chromosome 15
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describe the effect of genomic imprinting in turner syndrome
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if X inherited from the mother there is social problems
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recurrence risk to sibs in PWS if:
1. the affected child has a deletion or uniparental disomy 2. affected child has a mutation of the imprinting control center 3. if a parental chromosome translocation is present |
1. <1%
2. up to 50% 3. up to 25% |
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SRO is the regulatory region, AS-SRO controls wheter or not PWS-SRO is methylated. if AS-SRO is active, PWS-SRO is methylated and the affected ____________ only will transmit the disease.
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FATHER
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what percentage of SRO affected children from a carrier mother will be carriers?
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50%
*the sons will have a 50% chance to transmit the disease |
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AS can be caused by a mutation in what gene, where only mothers passing on the mutation will have affected children (50%)
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UBE3A
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what type of testing detects over 99% of patients with AS/PWS?
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DNA-based methylation testing for deletion in the region 15q11-13
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what cytogenetics test is best to detect large duplications, rearrangements, aneuplodies?
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high resolution G banded chromosomes for karyotyping
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what are the 3 types of probes for FISH?
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locus specific - labels a specific single gene
centromeric probe - labels a specifc pair of chromosomes chromosome painting probe - labels a specifc chromosome on the entire length |
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what type of FISH would be used to detect:
1. microdieletions 2.trisomeis, or large duplications |
1. locus specific
2. chromosome painting |
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what is the recurrence risk of downs if the mother is a carrier (robertsonian)?
non-disjunction? |
1/10
1/100 |
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what is the occurance risk of downs if the mother is less than 30?
over 40? |
1/1000
>1/100 |
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unbalanced rearrangments are ____________ so there will be no offspring
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reproductively lethal
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what are the 3 diseases that display anticipation and their inheritence patterns, and where they expand
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Huntingtons CAG autosomal dominant; expand in male
Fragile X syndrome CGG x-linked dominant; expand in female Myotonic Dystrophy CTG autosomal dominant; expands in female |
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the most common cause of mental retardation
the most common cause of genetic retardation the most common cause of inherited retardation |
EtOH
downs fragile X |
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why are females half as likely as males to be affected in
fragile X-syndrome |
difference in penetrance (50% in females)
|
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in fragile X mothers of transmitting males have a much lower proportion of affected sons than did the daughters of these males. Daughters of transmitting males are ________ affected. This is called "sherman's paradox"
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never, b/c it doesn't expand in males
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____________ are often progressive or do not manifest until adulthood
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mitochondrial disorders
|
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what tissues are most likely to be affected by mito disorders
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heart, CNS, sketal muscles b/c they relay on ox phos. these disease manifest by myopathies neuropathies, and encephalopathies
|
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what are 3 mitochondria disorders and which of them show heteroplasmy?
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LHON (Leibermans Hereditary Optic Neuropathy) - no heteroplasmy
MERRF (Myochlonicl Epilepsy and Ragged Red Fibers) - heteroplasmy MELAS (Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke like symptoms) - heteroplasmy |
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name the dz 95% of causes caused by one of 3 missense mutations in a mitochondrial protein (mt DNA protein complex I)
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LHON
|
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mitochondrial mosaicism is called?
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Heteroplasmy
|
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what is the mutation in MERRF and MELAS?
|
a single base change in mito tRNA that results in a change of codon specificity
**some mitochondrial DNA mutations (especially deletions) occur sporadically; therefore, the family history may not show evidence of maternal inheritance |
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steps to karyotyping
|
lymphocytes cultured
stopped in metaphase cells lysed protease used to unwide DNA Geimsa stained photo taken arranged in pairs |
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how do you know if a trait is 100% genetic?
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MZ twins 100% concordance, DZ twins 50%
|
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formula for heritability?
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H=2(Cmz-Cdz)
|
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below a certain genetic liability, no disease occurs even with an environmental trigger, above it dz results; this is called
|
threshold of liability
|
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average incidence of common malformation is?
|
1/1000
cleft lip and spina bifida |
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which has a lower risk of reoccurence if the dz has a higher prevalance in males.
An affected male or an affected female? |
an affected male b/c there is less genetic load (threshold of liability)
|
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how do you calculate recurrence risk for multifactorial disease
|
determined form empirica data
|
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relation of HLA haplotypes to dz and use of this info in genetic couseling is called
|
allele association and risk modification
|
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general pattern for isolated congenital anomaly
1. identical recurrence risk 2. 1st degree relative 3. 2nd degree relative 4. 3rd degree relative |
1. 30-40%
2. 3-4% 3. 0.5% 4. 0.1% (gen pop risk) |
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following a gen by analysis of iits proximity to makrer loci on the same chromosome is called?
|
linkage analysis
|
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what is the differnce b/w genotyping and gazplotyping?
|
haplotyping determins which one of each pair of alleles are in synteny
|
|
match the types of polymorphisms to how to assay them:
a. RFLP b. VNTR c. Microsatellites d. Singles nucleotide polymorphisms (SNPs) 1. DNA fingerprinting 2. southern blots and PCR 3. PCR 4. DNA microarrays, ASO, singl-base extension sequencing, |
1. (b)
2. (a) 3. (c) 4. (d) |
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what are the current markers of choic for linkagte studies
|
SNPs
|
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what genetic test can determin whether PWS/AS was cuased by a microdeletion, new mutation, or UPD
|
haplotyping
|
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_______% of nt bases are identical in humans, yet
_______ difference b/w any tow humans |
99.9%
3 million |
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a common allele means that 2 alleles have a frequency of greater than?
|
20%
|
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testing for the presence of specific mutation is what genetic testing?
|
targeted mutation analysis
|
|
mutation scanning is also called
|
exon scannaing
|
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what testing method is used if affected individual does not have a mutation detected by mutation analysis or for dz with a high proportion of rare alleles (family specific mutation)
|
targeted mutation analysis
|
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what method is a process to detec deletions/duplications of an entire exon, multiple exons or the whole gene that are typically not ID'd by seq analysis?
|
Quantitative PCR
|
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what testing method is used to detect heterozyogous deletion mutation and duplication mutations, and carriers of an AR disorder and X-linked disorders
|
quant PCR
|
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what is the difference b/ presymptomatic and predisposition
|
presymptomatic you ahve the mutation and you get the disease but if you have a predisposition, you are at a higher risk, doesn't mean you'll get it\
|
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what are 3 testing methods to detect variation at the DNA level?
|
sequencing
southern blot PCR |
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what are 2 testing methods to detect variation at the RNA level?
|
northern blot, RT-PCR
|
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what is a testing method to detect hemoglobinapathes and changes in protein structure
|
PROTEIN ELECTROPHORESIS
|
|
what is a testing method to detect protein abundance?
|
western blotting,
ELISA, immuno histochemistry |
|
what genetic testing method do you use to detect inborn errors of metabolism
|
biochemical assays - measures analytes, enzyme assays
|
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cytogenetics is changes in chromosome (# or structure) what genetic testing method is used to detect this?
|
special karyotyping
FISH G bnad karyotyping |
|
difference b/w southern blot and PCR
|
PCR has no probe, no blot, and detects smalldifferenes, but the pieces are small too
Southern blot uses a probe but it can detect lareger differeneces |
|
what are the most common polymorphisms?
|
SNPs
|
|
what is used to detect the allelic cause of Huntington Dz?
|
G8 RFLP
|
|
how are repeat expansion diseases detected by genetic testing methods?
|
by PCR followed by protein electrophoresis
|
|
what is the most common disease causing muation in DMD?
|
deletion in one or more of the exons on DMD gene that leads to less/no expression of dystrophin protein
|
|
a multiplex PCR of 9 exons is used to detect deletions in what gene?
|
DMD gene
**females will not be mosaic for dystrophin expression in muscles b/c cells are multinucleated and fused so it's all or none |
|
carrier testing for deletions are done by what testing methods?
|
RISH or quantitative PCR
|
|
what is the disease cuasing mutation oin SCA?
|
Glu6Val in the B globin gene
|
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what are two ways to screen for SCA
|
ASO (allele specific oligonucleotide) and protein electrophoresis
|
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what is the difference b/w the SE asian and black for of A thalassema ?
|
asian = --/aa (15-20% and they are called a-thal trait)
black = -a/-a (5% a thal trait; 45% are carriers aa/-a) |
|
what is the prevalence of B thal trait in blacks?
geek/italian/middle eastern? |
1/50
1/20 |
|
what is HB lepore?
|
type of b thal allele caused by unequal cross over of delta and beta chain that is functionally active but expressed at low levels due to fetal promotor
|
|
HbS/HbBo person would be what phenotype?
|
sickle cell
|
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in 45% of the causes of hemophilia they could not detect any mutations using sequencing of exons and intron/exon boundaries, in addition the mRNA looked normal, but the protein was missing why?
|
incorrect recombination in introons leading to nonsence muation due to inversion in sequce, so there was still mRNA (that's why nornthern blot was normal) but directions for translation was inverted creating a functional break in the template, i could be detected by protein electrophoresis, and western blot
|
|
what testing method would you use to detect a deletion of an entire locus?
|
FISH
|
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what is the gold std in detecting alteration in regulatory or coding sequences?
|
DNA sequencing
|
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a single base change that lead to a nonsense mutation would lead to a abnormality in what testing method?
|
Abn northern blot due to truncated mRNA
|
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point muations in noncoding regions could lead to a abnormality in what testing method?
|
abn southern blot due to interruption of resitiction site
|
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what could lead to normal southern and northern blots, but affect protein expression
|
missense mutation
|
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advanced paternal age is associated with increased incidence of what type of muations?
|
>45yo have increase risk for single gene mutations
|
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what dz has increase occurrence risk in SE Asians? Carrier freq?
|
a thal
1/5 ***1/20 for blacks (a-/a- type) |
|
what dz has increase occurrence risk in blacks? Carrier freq?
|
sickle cell
|
|
what dz has increase occurrence risk in whites? Carrier freq?
|
CF
1/25 |
|
what dz has increase occurrence risk in Mediterranians? Carrier freq?
|
b thal
1/20 ***(1/50 for blacks) |
|
what dz has increase occurrence risk in Ashkenazi Jews? Carrier freq?
|
TSD - AutoRes
1/20 canavan Dz - AutoRes 1/40 |
|
what is the dz mutation in Tay Sachs
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def in Hex A leads to accum of ganglioside
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what si the dz mutation in Canavan Dz?
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def in aspartoacylase leads to accum in NAcetylaspartic acid
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what is the inheritance pattern of DMD?
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x-linked, but 1/3 due to spon mutations
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what is the dz mutation in DMD and BMD?
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DMD is a deletion in the DMD gene leading to no dystrophin
BMD is a deletion in the DMD gene leading to reduced dystrophin |
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what is the inheritance pattern and dz mutation in MD?
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it is repeat expansion autoDom
mutation in mytonin protein kinases gene on Chrom 19 |
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what is the premutation range for MD?
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50-100 repeats
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what is the most common inherited bleedin disorder?
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von Willebrands Dz (autoDom)
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what is the affected protein in NF1 and what is it's function?
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Neurofibromin - negative regulator of Ras oncogenes
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what is the most common genetic cause of repeated pregnancy loss?
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balance chromosomal rearrangement leading to unbalance inheritance
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incidence of what type of disorders are increased with consanguinity and what is the risk of serious abnormality in mating b/w first cousins?
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AutoRec
6-8% (***double the 3-4% it is for the normal pop) |
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what maternal condition can lead to these symptoms in the baby?
cardiac and neural tube defects, SNS defects (hydrocephalus), renal anomalies, caudal regression syndrome |
Maternal pregestational diabetes (DMI)
***need proper control of sugars |
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what maternal condition can lead to these symptoms in the baby?
mental retardation (most common), microcephaly, heart defects (ToF), pre adn post natal growth def, miscarriage |
maternal PKU
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how do you treat maternal PKU for pregnancy?
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special diet prior to conception to keep maternal levels less than 4 mg/dL
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what do all these have in common?
alcohol (mental retardation), anticonvulsant meditations, accutane, lithium (CV abnormalities) |
all teratogens
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Autosomal Dominant
LDL receptor defect accelerated atherosclerosis-->zanthomas |
familial hypercholesterolemia
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autosomal recessive
B Glu6Val aplastic crisis, acute chest syndrome, vas-occlusive pain |
SCA
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DMD/BMD
type of inheritance mutation freq of it being inherited |
x-linked recessive
mutation in DMD gene (largest known human gene) 2/3 inherited from mother |
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NEURFIBROMATOSIS
1. inheritance 2. mutation 3. clinical |
1. autodom
2. NF1 gene on chrom 17 coding for neurofibromin (more common) or NF2 gene on chrom 22 (swannomas) 3. cafe au lait spots, neurofibromas |
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MARFAN SYNDROME
1. inheritance 2. mutation 3. clinical |
1. Autodom
2. fibrillin gene 3. mitral valve prolapse, dilation of aorta, tall, long extremities |
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PKU
1. inheritance 2. mutation 3. clinical |
1. autorecessive
2. Phe hydroxylase mutation (usually missence) 3. CNS defects, severe mental retardation, microcephaly, hyperactivity |
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GAUCHER's Disease
1. inheritance 2. mutation 3. clinical |
1. autosomal recessive MC lysosomal storage dz
2. GBA gene mutation dec level of glucocerebrosidase activity 3. erlenmeyarer flask deformity, anema, thrombocytopenia, leukopenia, bone/muscle pain |
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Trisomy 21
1. inheritance 2. mutation 3. clinical |
1. chromosomal
2. nondisjunction of chrom 21; 5% robersonian translocation 3. flat face, epicanthal folds, simian crease, low IQ, delays |
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Edwards Syndrome (trisomy 18)
1. inheritance 2. mutation 3. clinical |
1. chromosomal
2. extra 18 3. quad test low hCG, club hands, rocker bottom feet, horseshoe kidney, hernias |
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Patau Syndrome (trisomy 13)
1. inheritance 2. mutation 3. clinical |
1. chromosomal
2. nondisjuction, mosaic, partial (robertsonian translocation) 3. mental retardation, seizures, colboma, cleft, small eyes, head, extraf fibers, close set eyes, |
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Del22q Microdeletion syndrome VELOCARDIOFACIAL SYNDROME
1. inheritance 2. mutation 3. clinical |
1. aka diGeorge sequence
2. microdeletion of chrom 22 due to recom event in meiosis 1 3. penetrance 100% but highly variable expression; cleft palate, abnormal facies, thymic aplasia, cardiac defect, hypocalcemia, microdeletion @ 22 |
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FRAGILE X SYNDROME
1. inheritance 2. mutation 3. clinical |
1. x-linked dominant (no father to son)
2. expansion o f CGG repeats 3. learning/memory impairment, macroorchism in males, protruding ears, long face, arched palate, hyperextensible finger/thumb |
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TURNER SYNDROME
1. inheritance 2. mutation 3. clinical |
1. chromosomal
2. nondisjunction in gametogenesis, mosaicism, structural abnormalies 3. wide spaced nipples, hort, webbed neck, horseshoe kidney |
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KLINEFELTERS SYNDROME
1. inheritance 2. mutation 3. clinical |
1. chromosomal
2. gain of fuction 47XXY 3. most common cause of hypogonadism, tall height, shortest CAG repeats gets inactivated |
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APCKD
1. inheritance 2. mutation 3. clinical |
1. Autodom (common) and AutRec (rare)
2. mutation in PKD1 or 2 3. abd pain, hematuria, nocturia, flank pain, cysts in kidney |
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G6PD DEFICIENCY
1. inheritance 2. mutation 3. clinical |
1. x-linked recessive
2. Xq28 G6PD A - 1/10 black men affected 1/5 black females carriers G6PD Med - more severe (severely reduced half life) 3. oxidateive triggers result in oxidative stress maing heinzmbdoes, bite cells, and intravascular hemolysis leading to jaundice, anemia, hemoglobinuria (dark urine) |
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CYSTIC FIBROSIS
1. inheritance 2. mutation 3. clinical |
1. autosomal recessive
2. CFTR gene on crhomsome 7 delta 508 Cl channel malfunction 3. salty skin, failure to thrive, coughing, recurrent resp infections, greasy stools |
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HEREDITARY HYPER COAGULATION
1. inheritance 2. mutation 3. clinical |
1. Auto Dom
2. factor V leiden - single point mutation in gene that codes for factor V (white>latino>black>asian) Prothrombin G20210A - point muation in prothrombin gene, 1/2 as common as facter V leiden |
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HEREDITARY BREAST CANCER
1. inheritance 2. mutation 3. clinical |
1. auto dom
2. BRCA 1 and BRCA 2 3. whites have highest rates, BRCA1 is worse, 2 more common in men |
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B THALASSEMIAS
1. inheritance 2. mutation 3. clinical |
1. varies
2. can be splcing (most common B+), promoter mutations, and chain terminator mutations (Bo) 3. detect by Hb electrophoresis |
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A THALASSEMIAS
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1. deletion
2. silent carrier 1 del; trait 2 del; HbH 3 deletion; HbBart 4 deletions (hydrops fetalis - lethal w/o transfusion) 3. detect by Hb electrophoresis |