Topics 1 and 2 Patterns of inheritance; mutations; genetic testing procedures

Question 1

Autosomal dominant

Answer 1

1. When a single gene trait has the controlling alleles located on an autosomal chromosome, and the trait is expressed regardless of whether the person is homozygous or heterozygous for the dominant allele.
2. Found in approximate equal distribution between male and female family members.
3. Has no carrier status - the person with even one dominant allele expresses the trait; the trait appears in every generation with clear transmission from parent to child.
4. Unaffected people do not have the allele and have essentially zero risk for transmitting the trait to their children.

Question 2

Autosomal recessive

Answer 2

1. When a single gene trait has the controlling alleles located on an autosomal chromosome, and the trait is expressed only when both alleles are present (homozygous for the recessive allele).
2. Found in approximate equal distribution between male and female family members.
3. Carrier status - the trait often appears first in siblings rather than in the parents of affected children; may not appear in all generations of any one branch of a family.
4. Unaffected carriers can transmit the trait to their children if their partner is either a carrier or is affected.

Question 3

X-linked dominant - rare

Answer 3

1. Females do express the disorder in the heterozygous state and have a 50% chance of transmitting the trait with each pregnancy to children of either gender.
2. An affected father transmits the disorder to all of his daughters (who then express the disorder) and to none of his sons.

Question 4

X-linked recessive

Answer 4

1. The incidence of the trait is much higher among males in a family than among females.
2. The trait cannot be transmitted from father to son; transmission occurs from an affected father to all daughters (who will be obligate carriers) and from a carrier mother to both sons and daughters.
3. If no sons are born to carrier mothers, the trait may not be expressed overtly for many generations.
4. If no daughters are born to affected fathers who have children with noncarrier mothers, the trait is not transmitted further.

Question 5

Monogenic trait (single gene trait)

Answer 5

A trait whose expression is determined by the input of the two alleles of a single gene.

Question 6

Penetrance

Answer 6

1. How often, within a population, a gene is expressed when it is present. Higher penetrance = nearly 100% of people who have one allele will express the disorder.
2. Calculated by examining a population of people known to have the gene mutation and assessing the percentage of people in that population who actually express the condition coded by the gene.

Question 7

Expressivity

Answer 7

1. The degree of trait expression a person has when a dominant gene is present.
2. The gene is always expressed, but some people have more severe problems than do other people. Example: Neurofibromatosis - a few café au lait spots in the mild form, hundreds of protruding tumors in the severe form.

Question 8

Why are X-linked recessive disorders expressed at a higher rate in males than in females?

Answer 8

Because X gene alleles have no corresponding allele on the Y chromosome, any X-linked allele in a male is expressed as if it were a dominant allele, a condition known as hemizygosity. Males do not have a second X chromosome to balance the presence of a recessive gene allele on the first X chromosome.

Question 9

Polygenic trait

Answer 9

A trait or structure that involves the input of more than one gene.

Question 10

Allele

Answer 10

An alternative or variable form of a gene at a specific chromosome location.

Question 11

Codominant expression

Answer 11

A single gene trait in which two different dominant gene alleles are both expressed equally.

Question 12

Expression of any monogenic trait depends on _

Answer 12

Inheritance of dominant or recessive alleles and on whether the gene is located on an autosome or on a sex chromosome.

Question 13

Autosomes

Answer 13

The 22 pairs of human chromosomes that do not code for the sexual differentiation of the individual.

Question 14

Transmission

Answer 14

The term used to describe how a trait is inherited (passed) from one human generation to the next.

Question 15

Kindred

Answer 15

Extended family relationships over several generations.

Question 16

To draw supportable conclusions about trait transmission, at least _ family generations must be explored.

Answer 16

Three.

Question 17

The risk for an affected person who is heterozygous for the dominant allele to pass the trait to his or her child is _ with each pregnancy.

Answer 17

50%.

Question 18

The risk for an affected person who is homozygous for the dominant allele to pass the trait to his or her child is _ with each pregnancy.

Answer 18

100%.

Question 19

Examples of autosomal dominant traits

Answer 19

Blood type A; blood type B; achondroplastic dwarfism; type 2 diabetes; familial hypercholesterolemia; familial hyperlipidemia; Huntington disease; malignant hyperthermia; Marfan syndrome; polycystic kidney disease; polydactyly; von Willebrand disease.

Question 20

Examples of autosomal recessive traits

Answer 20

Blood type O; albinism; beta thalassemia; cystic fibrosis; phenylketonuria; sickle cell disease; Tay-Sachs disease.

Question 21

Examples of sex-linked recessive traits

Answer 21

Duchenne muscular dystrophy; fragile X syndrome; G6PD deficiency; hemophilia; red-green color blindness.

Question 22

Living people with disorders such as Huntington disease and achondroplasia are always _

Answer 22

Heterozygous for the mutated dominant allele, because the homozygous genotype appears lethal, with loss in utero or within the first 12 months after birth.

Question 23

The risk for children of two parents affected by an autosomal recessive disorder to also be affected is _

Answer 23

Close to 100%.

Question 24

About _ of the members of a family with an autosomal recessive trait will express the trait or disorder.

Answer 24

25%.

Question 25

Carrier

Answer 25

A person who is heterozygous for an autosomal recessive gene allele and does not fully express the trait or disorder, but can transmit the allele to his or her children.

Question 26

Normal human chromosome count

Answer 26

46 (23 pairs - 22 pairs of autosomes and 1 pair of sex chromosomes).

Question 27

X-linked recessive genes have _

Answer 27

Dominant expression in males and recessive expression in females.

Question 28

Female carriers of an X-linked recessive trait have a _ chance of transmitting the gene to their children with each pregnancy.

Answer 28

50%.

Question 29

X chromosome inactivation

Answer 29

Most of the genes on the X chromosome code for somatic cell functions, and females receive one X from each parent. During organ differentiation in the embryonic stage, the genes from one X chromosome are randomly inactivated, but some portion of the other parental genes remains in the form of a Barr body, and can still affect organ function.

Question 30

Genes

Answer 30

Sequence of nucleotides along the DNA of a chromosome that codes for a functional protein (ATCG).

Question 31

Genetics

Answer 31

Study of individual genes and their impact on relatively rare single gene disorders.

Question 32

Human genomics

Answer 32

Study of all the genes in the human genome together, including their interactions with each other, the environment, and the influence of other psychosocial and cultural factors.

Question 33

Polymorphisms

Answer 33

Small variations (one or two base pairs) of a gene which may not cause a disease by themselves, but may cause a disease in combination with other small variations, or in combination with environmental factors (e.g., hypertension).

Question 34

BRCA1 and BRCA2 are examples of _ genes.

Answer 34

Predisposition.

Question 35

4 basic genetic nursing responsibilities

Answer 35

1. Identify patients who will benefit from genetic interventions.
2. Provide genetic-based nursing interventions.
3. Communicate genetic information correctly, or be able to make referrals for patients.
4. Reflect on one’s own practice.

Question 36

Cystic fibrosis inheritance is _

Answer 36

Autosomal recessive.

Question 37

Neurofibromatosis inheritance is _

Answer 37

Autosomal dominant.

Question 38

A mutation on the _ gene is associated with the development of juvenile ALS, leading to a potential therapeutic target.

Answer 38

SIGMAR1.

Question 39

The _ gene is the first known gene to be required for sperm production in species ranging from insects to mammals.

Answer 39

BOULE.

Question 40

Gene locus

Answer 40

A specific location on a chromosome; often a specific gene.

Question 41

Phenotype

Answer 41

The observed expression of the genes of an individual (expression can be biochemical, physiological or morphological).

Question 42

Genotype

Answer 42

The genetic constitution of an individual; also, the alleles present at a particular locus.

Question 43

Achondroplasia

Answer 43

1. The most common cause of human dwarfism - autosomal dominant.
2. Mutation in the Fibroblast Growth Factor Receptor 3 gene (FGFR3).
3. Normal size trunk with short arms and legs.
4. Recurrence risk is low if parent is not affected, but 80% of people with achondroplasia have average height parents - their dwarfism is the result of a new FGFR3 mutation.
5. When 2 affected individuals mate (often dwarves prefer other dwarves): 50% chance of having an affected child; 25% chance of homozygous lethal; 25% chance of child with normal stature.

Question 44

Adult Dominant Polycystic Kidney Disease (ADPKD)

Answer 44

1. Autosomal dominant.
2. Adult onset disorder in which cysts form throughout the kidneys; causes progressive renal dysfunction and ultimately renal failure.
3. One of the most common inherited disorders in humans (1:300); accounts for 10% of all dialysis patients.
4. Symptoms: Abdominal pain, hematuria, polyuria, intense pain from kidney stones. Comorbid hypertension occurs in about 50% of cases.
5. Increased risk for subarachnoid hemorrhage, cerebral aneurysm, and stroke.

Question 45

ADPKD shows _ expression because less than 5% of nephrons become cystic.

Answer 45

Focal.

Question 46

Marfan syndrome

Answer 46

1. Autosomal dominant.
2. Connective tissue disorder in which a person is typically very tall, with long limbs and long thin fingers (arachnodactyly), and loose, hyperextensible joints.
3. The most serious complication is defects of the heart valves and aorta (aneurysm).
4. More than half of Marfan patients experience dislocation of the lens of the eye.

Question 47

Neurofibromatosis 1

Answer 47

1. Autosomal dominant.
2. Results from a mutation in the gene for neurofibromin on chromosome 17; about 50% of cases are due to a new mutation.
3. Neurofibromas, café-au-lait macules - six or more measuring 1.5 cm in their greatest dimension, freckling in the axillary and inguinal areas, sphenoid dysplasia (thinning of the cortex in long bones), Lisch nodules.

Question 48

Osteogenesis imperfecta

Answer 48

1. Autosomal dominant.

2. “Brittle bone” disease - defect in type I collagen gene.

Question 49

Phenylketonuria (PKU)

Answer 49

1. Autosomal recessive.
2. Mutation in phenylalanine hydrogenase (PAH) on chromosome 12 prevents the normal degradation of phenylalanine, which then accumulates in the tissues. Diagnosis is via blood tests in newborns; baby must have had at least 2 feedings.
3. Hyperphenylalaninemia is particularly toxic to the developing nervous system; therefore, untreated PKU can cause mental retardation.
4. Management is dietary restriction of phenylalanine intake.

Question 50

Cystic fibrosis

Answer 50

1. Autosomal recessive.
2. Usually caused by a deletion mutation on the cystic fibrosis transmembrane regulator (CFTR) gene, which regulates chloride ion channels.
3. Manifestations: Progressive pulmonary disease, elevated sweat chloride, meconium ileus, exocrine pancreatic insufficiency.

Question 51

Tay-Sachs disease

Answer 51

1. Autosomal recessive.
2. Lysosomal storage disorder caused by a lack of hexosaminodase A, the enzyme that breaks down fatty wastes.
3. Lack of the enzyme causes waste to accumulate in nerve cells.
4. Child appears normal at birth; deterioration of mental and physical abilities appears about 1 year after birth. The child becomes blind, deaf, and unable to swallow.
5. One in 27 Louisiana Cajuns are carriers for the Tay-Sachs gene.

Question 52

Women with PKU should start a restricted diet prior to _

Answer 52

Conception (due to the teratogenic effect of high levels of phenylalanine in maternal serum).

Question 53

Affected grandfather to affected grandson transmission through a carrier female intermediate is a characteristic of _ inheritance.

Answer 53

X-linked recessive.

Question 54

47,XXY

Answer 54

Kleinfelter Syndrome or aneuploidy.

Question 55

Hemophilia

Answer 55

1. X-linked recessive.
2. Clotting disorder that causes bleeding into soft tissues; caused by mutations in either factor VIII or factor IX.
3. Primarily males affected.

Question 56

Duchenne muscular dystrophy

Answer 56

1. X-linked recessive.
2. Mutation in the dystrophin gene; males have a 50% chance of being affected.
3. Manifestations: Fatigue, muscle weakness (begins in the legs and pelvis, but also occurs less severely in the arms, neck, and other areas of the body), progressive difficulty walking.

Question 57

Hypophosphatemic rickets

Answer 57

1. X-linked dominant.
2. Genetic defect in the handling of phosphate in the proximal tubules of the kidney.
3. Manifestations: Short stature, leg bowing, tooth anomalies.

Question 58

Rett syndrome

Answer 58

1. X-linked dominant.
2. The most severe form of autism that only affects girls.
3. Neurodevelopmental disorder - slowed growth, loss of movement and coordination, severe scoliosis.

Question 59

If a woman has a mitochondrial gene disorder, there is a _ chance that her children will inherit the disorder.

Answer 59

100%.

Question 60

Expert referral for patients with mitochondrial disorders should be made to _

Answer 60

Emory University.

Question 61

Dynamic mutations/trinucleotide expansion disorders

Answer 61

1. Tandem repeats of three base pairs (trinucleotides) that often change size upon transmission to children.
2. Normal people have the repeat; longer repeats are abnormal.

Question 62

Diseases caused by trinucleotide repeats

Answer 62

1. Fragile X syndrome.
2. Huntington’s disease.
3. Friedreich’s ataxia.
4. Myotonic dystrophy.

Question 63

Trinucleotide expansion disorders over generations - anticipation

Answer 63

1. Repeat expands with each successive generation.
2. Age of onset becomes younger with each successive generation.
3. Severity of disease increases with each generation.

Question 64

Huntington’s disease

Answer 64

1. Autosomal dominant.
2. Mutation is a triplet repeat expansion of CAG; causes death of cells in the caudate nucleus and an overproduction of the huntingtin protein, whose function is unknown.
3. Manifestations: Dementia, memory loss, chorea (random, jerky, uncontrolled movements).
4. Has a late age of onset (usually in 40s); diagnosis is with PCR.

Question 65

Huntington’s disease has _, meaning that every person with the gene will ultimately express the disorder.

Answer 65

100% penetrance.

Question 66

Fragile X syndrome

Answer 66

1. The most common heritable form of moderate mental retardation.
2. Trinucleotide repeat on the FMR1 gene.
3. Patients have behavior problems, hyperactivity and autistic features; a long face with a prominent jaw, large ears and macroorchidism. Lifespan is normal.

Question 67

Friedreich’s ataxia

Answer 67

1. Autosomal recessive.
2. Trinucleotide repeat results in loss of sensory ganglion cells, depriving the cerebellar column of the input needed to coordinate movement.
3. Manifestations: Dysarthria (slowness and slurring of speech), ataxia (impaired muscle coordination which starts in the legs and spreads to arms and trunk), heart problems, and muscle weakness/fatigue.

Question 68

Friedreich’s ataxia is associated with individuals of _ descent.

Answer 68

Cajun (but they usually have a less severe form with a later onset).

Question 69

Sickle cell anemia

Answer 69

1. Autosomal recessive.
2. Most common genetic disease of American Americans (1/700); caused by mutation in hemoglobin B subunit.
3. Not just an oxygen content problem - patients have skeletal problems, infarctions, and repeated infections.

Question 70

The only mutation that is responsible for sickle cell anemia is _

Answer 70

A valine substitution for glutamine on the hemoglobin B subunit.

Question 71

Glucose-6 phosphate dehydrogenase deficiency

Answer 71

1. X-linked recessive.
2. Affects about 1 in 10 African American males in the U.S.
3. Patients present with acute hemolytic episode or neonatal jaundice; diagnosed by measuring G6PD activity in red blood cells.
4. Often not seen until an environmental trigger aggravates the disorder - person will have anemic symptoms.
5. Triggers: Fava beans and moth balls (naphthalene).

Question 72

Disease phenotype - microcephaly and high pitched cat-like cry

Answer 72

Cri du chat syndrome.

Question 73

Disease phenotype - high mortality due to intracranial aneurysms

Answer 73

Adult dominant polycystic kidney disease.

Question 74

Disease phenotype - pancreatic insufficiency

Answer 74

Cystic fibrosis.

Question 75

Used to diagnose Turner syndrome

Answer 75

Karyotype or FISH.

Question 76

Used to detect carrier status for recessive disorders

Answer 76

Direct gene testing.

Question 77

Sometimes a person might carry a mutation such as BRCA1 but never develop the disease. What is the term for this phenomenon?

Answer 77

Incomplete penetrance.

Question 78

45,XO

Answer 78

Turner syndrome.

Question 79

Heterochromatin

Answer 79

Where the DNA is more condensed, and usually there is not much transcriptional activity. Some heterochromatin will remain condensed throughout the cell cycle.

Question 80

Euchromatin

Answer 80

This is where the “active” genes are - usually this region is much less condensed.

Question 81

46,XY

Answer 81

Normal male karyotype.

Question 82

Cytogenetic analysis can be done on _

Answer 82

Blood, amniotic fluid, chorionic villus samples (CVS), skin fibroblast cultures, bone marrow, or solid tumors.

Question 83

Monosomy

Answer 83

Absence of a single chromosome.

Question 84

Trisomy

Answer 84

An extra copy of a single chromosome.

Question 85

Karyotype

Answer 85

A photograph of the chromosomes from one cell.

Question 86

Aneuploidy

Answer 86

Any number of chromosomes that is not diploid; is the result of nondisjunction (failure of chromosome pairs to separate during cell division).

Question 87

Triploidy

Answer 87

3n or 69 chromosomes.

Question 88

Polyploidy

Answer 88

Any multiple of the haploid chromosome number other than the normal diploid number.

Question 89

Solid staining is most useful for _

Answer 89

Counting the number of chromosomes.

Question 90

G-banding is most useful for _

Answer 90

Recognition of banding patterns of each chromosome.

Question 91

Turner syndrome

Answer 91

1. 45,XO - only affects women.
2. Short stature; skeletal abnormalities; an early loss of ovarian function (premature ovarian failure) is very common. 30% of Turner patients have a webbed neck and a low hairline at the back of the neck. Hearts defects somewhat common.
3. Most girls and women with Turner syndrome have normal intelligence.

Question 92

Kleinfelter syndrome

Answer 92

1. 47,XXY - only affects men.
2. Males with infertility; small penis and testes; enlarged breasts; sparse facial and body hair; tall stature, long limbs; dull mentality and/or behavioral problems are common.

Question 93

5p-

Answer 93

Cri du chat syndrome (deletion of part of the short arm of chromosome 5).

Question 94

9;22 translocation is 100% diagnostic for _

Answer 94

Chronic myelogenous leukemia (CML).

Question 95

FISH is most useful for identifying _

Answer 95

Cytogenetic abnormalities such as trisomy 21 (Down syndrome).