Single Gene Disorders

Question 1

Autosomal dominant

Answer 1

Only one copy of the gene is required for the disease to be present - the trait appears in every generation

Question 2

Autosomal recessive

Answer 2

Two copies of the gene are required (one from each parent) for the gene to be expressed

Question 3

X-linked dominant

Answer 3

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

Question 4

X-linked recessive

Answer 4

Trait occurs almost only in males and females are carriers

Question 5

Mutations

Answer 5

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

Question 6

Genomic mutation

Answer 6

Missegregation of chromosome pairs (trisomies, etc)

Question 7

Chromosomal mutation

Answer 7

Structurally abnormal chromosome

Question 8

Gene mutation

Answer 8

Substitution, deletion, or addition

Question 9

Missense mutation

Answer 9

change in one nucleotide that changes the amino acid and then changes the protein that is expressed

Question 10

Nonsense mutation

Answer 10

Replaces a single nucleotide that changes the amino acid and causes the shortening of the protein

Question 11

Deletion mutation

Answer 11

Deletion of a single nucleotide, creating incorrect amino acid sequence and produces a malfunctioning protein

Question 12

Insertion mutation

Answer 12

Insertion of a single nucleotide that causes an incorrect amino acid sequence and produces a malfunctioning protein

Question 13

Frameshift mutation

Answer 13

Frameshift of one DNA base results in abnormal amino acid sequence

Question 14

Repeat expansion mutation (myotonic dystrophy)

Answer 14

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

Question 15

Cystic Fibrosis

Answer 15

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

Question 16

Congential Myotonic Dystrophy

Answer 16

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

Question 17

Clinical features of myotonic dystrophy

Answer 17

hypotonia
poor feeding
facial diplegia
clubfoot
cataracts
respiratory difficulties
delayed motor development

Question 18

Diagnosis of myotonic dystrophy

Answer 18

History and clinical manifestations
Electromyography
Muscle biopsy
serum creatinine kinase

Question 19

Osteogenesis imperfecta

Answer 19

1:5000-10000 live births

90% are autosomal dominant

Can be caused by a new mutation

Four types

Question 20

OI Type 1

Answer 20

Most common
Bones fracture easily
Blue sclera
Dental problems
Hearing loss beginning in 20s and 30s
Tendency toward spinal curvatures

Question 21

OI Type 2

Answer 21

Newborns are severely affected - generally lethal
May fracture in utero
Small stature, small chest and underdeveloped lungs

Question 22

OI Type III

Answer 22

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

Question 23

OI Type IV

Answer 23

Usually mild, postnatal onset
Variability of expression
Dentinogenesis imperfecta (gray/yellow translucent teeth)
Hearing loss may occur
Spinal curvatures
Loose joints

Question 24

Achondroplasia

Answer 24

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

Question 25

Expressivity

Answer 25

Severity of disease can vary based on how much gene is expressed

Question 26

Penetration

Answer 26

have the gene but what is the possibility that gene has any outward expression - can be dependent on expressivity

Question 27

Hemophilia A

Answer 27

Factor VIII deficiency
most common form
x-linked recessive
1:10000 male births
Gene lies at Xq28

Question 28

Hemophilia B

Answer 28

Factor IX deficiency

x-linked recessive

variable expression

Question 29

Infantile/Childhood Polycystic Kidney Disease

Answer 29

1:6000-14000 live births

Autosome recessive

Chromosome 6p

Multiple bilateral grape-like cysts that enlarge the kidney, compressing and eventually replacing functional tissue