Single Gene Disorders Flashcards
Autosomal dominant
Only one copy of the gene is required for the disease to be present - the trait appears in every generation
Autosomal recessive
Two copies of the gene are required (one from each parent) for the gene to be expressed
X-linked dominant
Females can be carriers, males cannot
Affected males will give the gene to all daughters but no sons.
Affected mothers who are heterozygotes will transmit to half of their offspring
Affected mothers who are homozygotes will transmit to all their offspring
X-linked recessive
Trait occurs almost only in males and females are carriers
Mutations
Permanent change in the base sequence or arrangement of bases in the DNA
Can have no effect, a harmful effect (genetic disease) or a beneficial effect
Genomic mutation
Missegregation of chromosome pairs (trisomies, etc)
Chromosomal mutation
Structurally abnormal chromosome
Gene mutation
Substitution, deletion, or addition
Missense mutation
change in one nucleotide that changes the amino acid and then changes the protein that is expressed
Nonsense mutation
Replaces a single nucleotide that changes the amino acid and causes the shortening of the protein
Deletion mutation
Deletion of a single nucleotide, creating incorrect amino acid sequence and produces a malfunctioning protein
Insertion mutation
Insertion of a single nucleotide that causes an incorrect amino acid sequence and produces a malfunctioning protein
Frameshift mutation
Frameshift of one DNA base results in abnormal amino acid sequence
Repeat expansion mutation (myotonic dystrophy)
Repeated trinucleotide set that continues to repeat at greater lengths with additional generations
Adds a string of incorrect amino acids to the protein and creates dysfunction
Cystic Fibrosis
Most common single gene disorder in North America - Autosomal recessive
1:2500 Caucasians
1:11500 Hispanics
1:14000 Blacks
1:30 caucasians are carriers
Chromosome 7q
Defect in production of CFTC - lack of conductor prevents chloride from entering cells, resulting in thick, sticky mucous that clogs ducts or tubes
Blocks airways, impedes infection fighting, blocks digestive enzymes from reaching intestines, excessive amount of salt loss in sweat
10% present in newborn period with meconium ileus
Newborn screen test for potential CF by testing for increased levels of trypsinogen
Sweat chloride is a definitive diagnosis
Congential Myotonic Dystrophy
1:7500 live births
Autosomal dominant with anticipation expression: Mother may show slight symptoms but children show increased severity
Progressive muscle weakness and wasting
Delayed relaxation of voluntary muscles after contraction
Increased number of triplet repeats on the gener - found on chromosome 19
Encodes protein kinase found in skeletal muscle
Clinical features of myotonic dystrophy
hypotonia
poor feeding
facial diplegia
clubfoot
cataracts
respiratory difficulties
delayed motor development
Diagnosis of myotonic dystrophy
History and clinical manifestations
Electromyography
Muscle biopsy
serum creatinine kinase
Osteogenesis imperfecta
1:5000-10000 live births
90% are autosomal dominant
Can be caused by a new mutation
Four types
OI Type 1
Most common
Bones fracture easily
Blue sclera
Dental problems
Hearing loss beginning in 20s and 30s
Tendency toward spinal curvatures
OI Type 2
Newborns are severely affected - generally lethal
May fracture in utero
Small stature, small chest and underdeveloped lungs
OI Type III
Isolated family incidents
Small in stature
Fractures at birth very common
May have some in utero
Severe early hearing loss
Barrel shaped rib cage
Blue sclera may be present
OI Type IV
Usually mild, postnatal onset
Variability of expression
Dentinogenesis imperfecta (gray/yellow translucent teeth)
Hearing loss may occur
Spinal curvatures
Loose joints
Achondroplasia
Most common growth related defect
1:25000 live births
Dwarfism
Mutation of gene encoding fibroblast growth factor receptor 3 (FGFR3)
Found on chromosome 4p
Overexpression
