Genetics-Midterm Review

Question 1

Is 45, XY, -13, -15, +t(13,15) balanced or unbalanced?

Answer 1

Balanced. Even though you lose the p arm of a chromosome, it doesn’t have significant genetic information on it.

Question 2

Can Down Syndrome run in the family?

Answer 2

Although most cases are sporadic, you can carry a genetic risk of Robertsonian location involving chromosome 21 that can cause heredity Down syndrome.

Question 3

Horizontal transmission pattern

Answer 3

AR, associated with consaguinity

Question 4

Vertical transmission pattern

Answer 4

AD

Question 5

No father to son transmission, all daughters of affected fathers are carriers

Answer 5

X-linked recessive, more males are affected and generation skipping will be seen.

Question 6

Vertical transmission, no father to son transmission and father transmits disease to all daughters.

Answer 6

X-linked dominant, more females are affected and males are often inviable.

Question 7

Carrier frequency when q is small?

Answer 7

When q is small, p=1 and carrier frequency = 2q.

Question 8

A 4-year-old boy presents to the physician’s office with coarse face, short stature, stiffening of the joints, and mental retardation. His parents, a 10-year-old sister, and an 8-year-old brother all appear unaffected. The patient’s mother is pregnant. She had a brother who died at 15 years of age with similar findings that seemed to worsen with age. She also has a nephew (her sister’s son) who exhibits similar features. Based on the probable mode of inheritance, which of the following is the risk that her fetus is affected?

Answer 8

1) What is the inheritance pattern? X-linked recessive. 2) Who are obligate heterozygotes? I-2, I-4 3)What is the risk of II-5 of inheriting disease allele? 50% 4) What is the chance of II-5 being male? 50% 5) .5 * .5 = 25% chance of being affected.

Question 9

Mr. Smith is affected with Crouzon syndrome (123500) and has craniosynostosis (i.e., premature closure of the skull sutures) along with unusual face that includes proptosis secondary to shallow orbits, hypoplasia of the maxilla, and a prominent nose. His son and brother are also affected, although two daughters and his wife are not. Mr. and Mrs. Smith are considering having another child. Their physician counsels them that the risk that the child will be affected with Crouzon syndrome is which of the following?

Answer 9

1) What is the inheritance pattern? AD 2) What is the change of II-4 inheriting the disease allele? 50%. 3) What is the total risk? 50%.

Question 10

A woman with cystic fibrosis marries her first cousin. What is the risk that their first child will have cystic fibrosis?

Answer 10

1) What is the inheritance pattern? AR 2) Who are obligate heterozygotes? II-3 and II-4 3) What is the chance of I-1 or 1-2 being a carrier? 100% 4) What is the chance of II-2 being a carrier? 50%. 5) What is the chance of III-1 being a carrier? 50%. 6) What is the chance of the child being a homozygote if the mother is affected and the father is a heterozygote? 50%. What is the total risk? .5 *.5 *.5 = 1/8.

Question 11

A child is evaluated by an ophthalmologist and is found to have retinitis pigmentosa, a disorder characterized by pigmentary granules in the retina and progressive vision loss. The pedigree below is obtained and the family comes in for counseling. What is the risk for individual II-2 of having an affected child if he mates with an unrelated woman?

Answer 11

1) What is the inheritance pattern? AR 2) What happens if a homozygote mates with unrelated individual? All children are carriers and virtually 0 risk of having an affected child

Question 12

A different family with retinitis pigmentosa is encountered, and the pedigree shown below is documented. What is the risk that a son born to individual III-3 would be affected?

Answer 12

1) What is the inheritance pattern? X-linked recessive 2) Who are the obligate heterozygotes? I-1, II-1 and II-3. 3) What is the chance of III-3 being a carrier? 50% 4) What is the chance that her son inherits the disease if she is a carrier? 50% 5) Total risk? 1/2 * 1/2 = 1/4

Question 13

Waardenburg syndrome (193500) is an autosomal dominant condition that accounts for 1.4% of cases of congenital deafness. In addition to deafness, patients with this condition have an atypical facial appearance, including lateral displacement of the inner canthi (eye corners), hypertelorism (widely spaced eyes), poliosis (white forelock), and white patches of skin on the ventral midline (partial albinism or piebaldism). A mother has Waardenburg syndrome, her husband is unaffected, and they plan to have a family with three children. What is the probability that one of the three children will be affected?

Answer 13

1) What is the inheritance pattern? AD 2) What is the chance II-1 being affected and II-2, II-3 being unaffected? 1/2 * 1/2 * 1/2 = 1/8. This is the same chance for each child being affected with no affected siblings. 3) What is the chance of II-1 or II-2 or II-3 being affected when the other children are unaffected? 1/8 + 1/8 + 1/8 = 3/8.

Question 14

In a family with Charcot-Marie-Tooth disease (CMT), affected individuals are tested by restriction analysis of the DNA using sites flanking the CMT gene on chromosome 17. The results show one large abnormal fragment and one smaller fragment that is seen in controls. What is the probable inheritance mechanism in this family?

Answer 14

Since you need two alleles, you know it is autosomal dominant.

Question 15

Allelic heterogeneity

Answer 15

Different mutations in the SAME gene

Question 16

Locus heterogeneity

Answer 16

Mutations in DIFFERENT genes that cause the same disease.

Question 17

Mutation you would suspect in AD disease w/no family history

Answer 17

New mutation

Question 18

Inheriting the mutant gene but no symptoms

Answer 18

Incomplete penetrance

Question 19

Mutation you would suspect in AD inherited by 2+ kids w/no family history

Answer 19

Germline (gonadal) mosaicism. Mitotic divisions of gametes w/mutations = some kids affected and some not.

Question 20

Pleiotropy

Answer 20

Several organs affected by mutation

Question 21

Expressivity

Answer 21

Same mutation affects different individuals in different ways

Question 22

A patient with the Marfan syndrome (154700) is evaluated at a clinic. He is noted to have a tall, thin body habitus, loose joints, and arachnodactyly (spider fingers). Ophthalmologic examination reveals lens dislocation. Echocardiogram reveals dilation of the aortic root. A family history reveals that the patient’s parents are medically normal, but that his paternal grandfather and great-grandfather died in their forties with lens dislocation and dissecting aortic aneurysms. A sister is found to have a similar body habitus, dilation of the aortic root, and normal lenses. The different findings in these family members with the same disease are best described by which of the following terms?

Answer 22

Same family members w/same mutation w/o skipped generation = variable expressivity.

Question 23

Polycystic kidney disease (1739000) is a significant cause of renal failure that presents from early infancy to adulthood. Early-onset cases tend to affect one family member or siblings, whereas adult-onset cases often show a vertical pattern in the pedigree. Which of the following offers the best explanation of these facts?

Answer 23

Same disease can be caused by mutation in two different genes. You expect two different inheritance patterns with two different mutations, so this would be locus heterogeneity.

Question 24

Anticipation

Answer 24

Every generation has worse symptoms due to trinucleotide repeats

Question 25

X chromosome inactivation

Answer 25

Random inactivation of one X in females

Question 26

Mitochondrial inheritance

Answer 26

Maternal inheritance and heteroplasmy (multiple types of inherited mitochondria)

Question 27

Genomic imprinting

Answer 27

Parent-of-origin gene expression due to genetic imprinting and silencing.

Question 28

Females occasionally have symptoms of X-linked recessive diseases such as Duchenne muscular dystrophy, hemophilia, or color blindness. Which of the following is the most common explanation?

Answer 28

Somatic mosiacism. All females are natural mosaics for the X chromosome and can express autosomal recessive disorders.

Question 29

Individuals II-5 and III-5 have a rare mitochondrial disorder. Who are all the other members of this pedigree likely to be at risk of having this mutation (even though they may be asymptomatic)?

Answer 29

I-2, II-1, II-3, II-7, III-3, III-4 from maternal mitochondrial inheritance

Question 30

An infant with severe muscle weakness is born to a mother with mild muscle weakness and myotonia. The mother’s father is even less affected. The worsening of symptoms could be explained by

Answer 30

Unstable trinucleotide repeats

Question 31

All of the following are examples of epigenetic regulation or modification except: histone acetylation, X-chromosome inactivation, genomic imprinting, triplet repeat expansion and Barr body formation?

Answer 31

Triplet repeat expansion, this directly affects DNA.

Question 32

Hardy-Weinberg assumptions

Answer 32

Large population, random mating, no mutation, migration or selection.

Question 33

Hardy-Weinberg equations

Answer 33

*

Question 34

If II-3 has PKU, an AR disorder present in 1/10,000 children, what is the risk for III-1?

Answer 34

What is the chance of II-4 being a carrier? 2/3. What is the risk of II-5 being a carrier? 2pq. q^2 = 1/10,000 so q = 1/100. p = 1- q so p = 99/100. 2pq = 1/50. What is the risk for III-1? (2/3)(1/50)(1/4) = 1/300

Question 35

What is linkage?

Answer 35

Genes on the same chromosomes are physically linked and segregate together. However sometimes recombination occurs and they get separated in the progeny.

Question 36

DNA analysis is performed on a family because the second child has propionic acidemia, an autosomalrecessive disease. The parents desire prenatal diagnosis, and the fetal DNA is also analyzed for polymorphic alleles A and B that are linked to the causative mutation. The results are shown below. Which of the following risk figures reflect the risk of the fetus being affected before and after testing?

Answer 36

Before testing = 1/4. After testing: they analyze the linked loci that have alleles A and B which both carry gene X. These alleles are located close to the disease gene and can be inherited together, so if the child is A/B he has a 1/4 chance of inheriting the disease (see below).