SINGLE GENE DISORDER Flashcards
complete set of chromosomes but a problem in a single gene in a single chromosome
Single Gene Disorder
what are the modes of inheritance in single gene disorder?
- Autosomal Dominant
- Autosomal Recessive
- X-linked
- Genetic disorders caused by genes on the autosomes in which a single abnormal allele is sufficient to cause disease despite the presence of normal alleles
Autosomal Dominant Diseases
how are genes inherited in autosomal dominant diseases?
- randomly
- 50-50% chance
- can affect both sexes and can appear in every generation
- autosomal dominant trait with complete penetrance
- most common form of human genetic dwarfism
Achondroplasia
chromosome affected in achondroplasia
short arm of chromosome 4 (4p16)
gene affected in achondroplasia
FGFR3 - Fibroblast-Growth Factor Receptor Gene 3
main characteristic of Achondroplasia
Short-limbed dwarfism and macrocephaly
examples of autosomal dominant diseases
- Achondroplasia
- Charcot-Marie Tooth Disease
- falls under the classification of diseases called Hereditary Motor and Sensory Neuropathies (HMSN) which causes motor and sensory neuropathies
- most common autosomal dominant disorder in humans
Charcot-Marie Tooth Disease
chromosome affected in CMT disease
Short arm of Chromosome 17
gene affected in CMT disease
CMT Type 1A
abnormality of CMT Type 1A
producing excess Peripheral Myelin Protein
main characteristics of CMT disease
- high arched feet
- nerve demyelination
genetic disorders caused by genes on the autosomes in which the disorder is caused by having two disease-causing copies of a gene
Autosomal Recessive Diseases
how are genes inherited in autosomal recessive diseases?
an individual who has inherited 2 abnormal alleles at a given locus by receiving 1 mutant allele from each parent
if both parents are carriers of an autosomal recessive disease:
- 25% chance with normal allele (normal)
- 50% chance with only 1 abnormal allele (carrier)
- 25% chance with 2 abnormal alleles (abnormal)
diseases under autosomal recessive
- cystic fibrosis
- hereditary hemochromatosis
- most common fatal autosomal recessive disorder of Caucasian children
- a multisystem disorder affecting the cells that produce mucus, sweat, saliva, and digestive juices
Cystic Fibrosis
chromosome affected in cystic fibrosis
long arm of chromosome 7
gene affected in cystic fibrosis
CFTR gene — Cystic Fibrosis Transmembrane Conductance Regulator Protein
person must have ? mutant CFTR allels to develop the disease
two
if CFTR does not function correctly:
- CFTR channel won’t be able to move chloride thus resulting to no release of chloride leading to no attraction of water
signs and symptoms of cystic fibrosis
- Chronic lung infection
- Pancreatic insufficiency
- Respiratory failure
most serious complication for cystic fibrosis
respiratory failure
- characterized by excessive deposition in healthy tissue
- causes pancreas, liver, and skin damage as well as heart disease and diabetes
Hereditary Hemochromatosis
affected individuals absorb approximately ? of iron, as normal people would absorb approximately ? of iron
3-4 mg/day, 1-2mg/day
chromosome affected in hereditary hemochromatosis
long arm of chromosome 6
gene affected in hereditary hemochromatosis
Hemochromatosis type 1 gene (HFE)
functions of HFE
- regulated the amount of iron absorbed from food
- but once mutated, it results in no regulation and constant absorption occurs
early symptoms of hereditary hemochromatosis
- weakness
- lethargy
- joint pains
- abdominal pain
treatment for hereditary hemochromatosis
- Phlebotomy
- Avoiding ferrous, mineral supplements, excess vitamin C, or uncooked seafood
mutant allele resides on the X-chromosome
X-linked diseases
carriers of x-linked diseases, with 1 normal and 1 mutant allele but typically not affected
Females
receiving the mutant allele from their mothers, having only 1 X chromosome; thus always affected by X-linked chromosome
Males
all daughters of affected males are ? of a mutant allele
carriers
carrier female have: (chances)
- 25% chance — normal allele son
- 25% chance — affected son
- 25% chance — carrier daughter
- 25% chance — normal allele daughter
x-linked mutation are almost always (dominant/recessive)
recessive
genetic mutations transmitted from an affected father to daughters:
- unaffected sons
- carrier daughters
genetic mutations transmitted from a carrier daughter to offspring
- daughter’s son has a 50% chance of inheriting the mutation
- daughter’s daughter has a 50% chance of being carriers
genetic mutation is almost (always/never) transmited from an affected father to a son
never
diseases under x-linked diseases
- hemophilia A
- duchenne muscular dystrophy
- fragile X syndrome
- x-linked recessive bleeding disorder
Hemophilia A
chromosome affected in hemophilia A
long arm of X chromosome band 28 (Xq28)
gene affecting hemophilia A
Factor 8 (deficiency of Factor 8 Xq28)
- characterized by progressive skeletal muscle wasting
- most common severe neuromuscular disease in humans
Duchenne Muscular Dystrophy
onset of DMD
before 3 years old
chromosome affected in DMD
short arm of chromosome X, band 21 (Xp21)
Xp21 encodes the protein ?
Dystrophin
functions of dystrophin
- transfers the force of muscle contractions from inside muscle cells to outside cell membranes
- resuting to ineffective growth and contraction of muscles leading to a series of manifestations, signs, and symptoms
main characteristics of DMD
- thick lower leg muscles (muscle is mostly fat and not strong)
- tight heel cord (contracture) child may walk toes
- weak muscles in front of leg cause “foot drop” and tip toe contractures
one of the most common inherited form of mental retardation
Fragile X Syndrome
Site of genetic disorder in fragile X
Chromosome X, long arm, band 27.3 (Xq27.3)
cause of Fragile X syndrome
- due to expansion of CGG repeats in 5’ untranslated region
- hypermethylation of the CGG region leads to FMR1 gene silencing
normal CGG repeats
6-45 repeats
Intermediate CGG repeats (gray zone, little symptoms)
46-54
pre-mutation CGG repeats
55-200; leads to ADHD or autism
full mutation CGG repeats
more than 200 repeats; leads to hypermethylation
characteristics of fragile X syndrome
- shows a gap or break in the structure of the X chromosome
- clinical feaatures worsen with each generation (anticipation)
- affects only male
main characteristics of Fragile X syndrome
- broad forehead
- elongated face
- large everted earch
- mitral valve prolapse
- mental retardation
20% cytologically and clinically normal but may transmit the disease to all his daughters and to affected grandchildren
carrier males
brothers of transmitting males are at ?% risk of having mental retardation
9%
grandsons of transmitting males have ?% risk
40%
?% of carrier females are affected and are mentally retarded
50%
- rare
- regulary expressed in heterozygotes (pedigree pattern is similar to autosomal dominant)
- females can be affected
X-linked Dominant Diseases
x-linked dominant disease affected males have: (offspring)
normal sons and abnormal daughters
children (male and female) of carrier mothers have a ?% chance of inheriting x-linked dominant diseases
50%
