Genetic Disorders Flashcards
Hurler Syndrome
Type, Gene, Symptoms, Rx
Autosomal Recessive
Gene: alpha-L-Iduronidase
Tay- Sachs:
type
What gene?
Build up of what?
Mutation Type and Result?
Autosomal Recessive
Gene: HexA
Build up of GM2 gangliosides leading to neuron damage
Mutation: 4 base insertion causing frameshift mutation. Premature stop codon and truncated protein
Cystic fibrosis
Type
Gene
Mutation type
Result
Autosomal Recessive
gene: CFTR
Mutation type: 1 amino acid lost, but in-frame mutation
Result: prevents CFTR chloride channel. Results in thick mucus sections because water isn’t attracted.
Sickle Cell Disease
Type
Mutation type
Autosomal Recessive
Mutation: wrong amino acid, (A to T)
Beta-Thalassemia
Type
Mutation type
Autosomal recessive
Point mutations decreasing production of beta globin (hemoglobin)
Hereditary hemochromatosis
Type
Gene
Mutation type
Whos affected
Autosomal Recessive
Gene: HFE (high iron)
Mutation: single missense resulting in iron overload
Who is affected? adult males more commonly affected
Huntington disease
Type:
Gene:
Autosomal dominant
Gene: HD, trinucleotide repeat expansion
Achondroplasia
Type:
Gene:
Autosomal dominant
Gene: FGFR-3, glycine to arginine missense, gain of function
Neurofibromatosis Type 1
Type
Gene
Type: autosomal dominant
Gene: NF1, nonsense point mutation resulting in shortened protein
Marfan Syndrome
Type
Gene
Autosomal dominant
Gene: FBN1, elastic fibers in connective tissue
Lesch - Nyhan Syndrome
Type
Gene
X-linked recessive
Gene: HGPRT - involved in purine recycling. Deficient HGPRT results in overproduction of uric acid
Duchenne muscular dystrophy
Type
Gene
mutation type
X-linked recessive
Gene: dystrophin (muscle fibers, largest human gene)
Mutation type: deletion leading to frameshift.
Milder cases have mutations without frame shift (becker) and protein is partially active
Hemophilia B
Type
males or females?
effect
mutation
X linked recessive
Affects males, females have second working X chromosome
Effect: deficiency of factor IX
Mutation: point mutation in promotor region of gene, A to G transition alters transcription factor of factor IX gene
Gowers sign
results from weakness of lower limbs
Use arms to “climb” up the legs to elevate the torso.
Rett syndrome
Type
Gene
variation of Sx
Male or female
X linked dominant
Gene: MeCP2
Variation in females due to skewed x-inactivation patterns
Generally not transmitted through families
Lethal in males
Fragile X Syndrome
Type
Gene
male or female
X linked dominant
Gene: FMR1, CGG repeat expansion in promotor region
More severe in males
Anticipation observed in later generations due to trinucleotide repeat expansion when female carriers pass the trait.
Langer mesomelic dysplasia and Leri-Weill dyschondrosteosis
Type
Mutation
Y chromosome disorder
mutation in pseudoautosomal region of SHOX gene
Swyer syndrome
Type
effect
Y chromosome, SRY gene disorder
Effect: genotypic male develops as a female
46 XX testicular disorder of development
Type
effect
Y chromosome disorder, SRY translocation onto X chromosome
Effect: individuals develop as male, with similar sx to kinefelter
Mitochondrial diseases
CEPO Kearns-Sayre Leigh LHON MERRF MELAS Person Syndrome
Phenylketonuria (PKU)
Type
Gene
Sign
Treatment
Autosomal recessive
Gene: PAH
Signs; phenylalanine and phenylketones in blood. Phenylketones in urine
Treatment: restrict dietary phenylalanine. if caught early, neurological damange can be mitigated
PKU: causes of intellectual disability
high levels of phenylalanine and phenylketones directly toxic to brain
Excess phenylalanine saturates lare neutral amino acid transporter at BBB, leading to excess of phenylalanine in brain and preventing other AAs from entering
Failure to produce adequate dopamine and epi due to lack of tyrosine
Origin of Trisomy 21
95% of cases due to mother’s nondisjunction of chromosome 21
5% due to robertsonian translocation
Trisomy 18 (Edward Syndrome)
Origin
Sxs
Nondisjunction of chromosome 18 in mother
Sx: intellectual disability low weight diaphragmatic hernia heart defects small eyes, mouth, receding jaw kidney defects clenched fists rocker bottom feet
trisomy 13 (Patau syndrome)
Origin
Sx
Origin: 95% nondisjunction in mother. 5% Robertsonian translocation
Sx: intellectual disability Microcephaly, holoprosencephaly postaxial polydactyly cleft lip/palate small eyes, large triangluar nose deafness
Turner syndrome
Cause
Sx
Treatment
45, X
Cause: one X chromosome, so only 1 copy of PAR1 and PAR2 genes
Sx: short stature, learning disabilities, braod neck, visual impairments, kidney abnormalities, ovarian dysgenesis and lack of secondary sexual characteristics
Treatment: growth hormone and estrogen therapy
Klinefelter Syndrome
Origin
Sx
Treatment
47, XXY
Sx: often SUBTLE
Treatment: testosterone therapy, speech therapy, physical therapy
Exons
coding regions that contain DNA sequence that translates to the final protein product
Introns
non-coding regions that contain regulatory information and can be removed by splicing
Molecular fingerprint
uses polymorphisms to identify an individual. identifies using the number of repeats in a sequence.
CODIS is used by the FBI to search a set of 15 VNTR loci
Everyone has 2 sets of chromosomes with their own repeat polymorphism pattern
STRP
2-5 bp
VNTR
14-500 bp
CNV
2 million bp
Paternity testing
uses VNTR analysis and compares bands of potential fathers to child.
If no bands are shared, the individual is not the father.
Nonsense mutation
introduces new stop codon
silent sense mutation
base change that doesn’t alter the amino acid
