5. Principles of Genetic Inheritance

Question 1

Where would you find the centromere in a metacentric chromosome?

What about a submetacentric chromosome?

What about an acrocentric chromosome?

What is special about acrocentric chromosomes?

Answer 1

The center

“just off” from center

Very close to one end, such that very little material is above/below it.

You can lose the genetic material on one side and still be ok (in some cases).

Question 2

What is the normal human karyotype?

Answer 2

46,XX or 46,XY

Question 3

In the karyotype: 46,XX, t(4,13)(q12:q14)

What is the underlined section?

Answer 3

The location of a translocation (in this case from chromosome 4 to 13)

Question 4

Define “Lyonization”

Answer 4

The random choice of which X chromosome will be activated.

More commonly called X-Inactivation

Question 5

Define Robertsonian Translocation

Answer 5

Where the long arm of TWO acrocentric chromosomes kicks off their tiny short arms and combine into one long chromosome.

Question 6

Chronic Myelogenous Leukemia is associated with what specific translocation?

What is the name of the resulting chromosome?

What type of translocation is that?

Answer 6

t(9:22) placing BCL and ABL together

The Philadelphia Chromosome

Reciprocal

Question 7

What is an inactivated X chromosome called?

Answer 7

A Barr Body

Question 8

Define Mosaicism

Answer 8

When, in a given patient, one of their cells has one set of genes, and another cell in their body has a different set of genes - or more or fewer genes.

Question 9

What is the genotype for a patient with Turner Syndrome?

What are the basic symptoms?

Answer 9

45,XO (Absent Y, so femaie)

• Short stature
• Many do not undergo puberty without HRT
• Ovarian hypofunction
• Webbed neck
• CV defects

Question 10

What is the genotype for a patient with Klinefelter Syndrome?

What are the primary symptoms?

Answer 10

47,XXY

Gynecomastia

Tall stature

Infertility

Low muscle mass

Question 11

For Down’s Syndrome

What is the basic cause?

What translocation can cause this disease?

What is the most common karyotype?

Answer 11

Autosomal Trisomy (possibly non-disjunction)

Robertsonian translocation can cause the disease (extra 21st chromosome material comes from the long arm of another chromosome sticking on, not a whole other chromosome.)

47,XY +21 (The +21 means an extra 21’s chromosome; trisomy 21. The other chromosomes are normal)

Question 12

Some genes are only expressed when they come from your mother or your father. What makes this happen?

When does this tag get put on?

Answer 12

Methylation of the genetic material - Called Genomic Imprinting

When you make a gamete. (The tags from your mother and father are taken off, and your new tags (father if you’re male, mother if you’re female) are put on.)

Question 13

Prader-Willi and Angelman syndromes are both due to the same deletion on Chromosome 15. What determines which disease a patient gets?

Answer 13

It depends on which gene is expressed.

Paternal Chromosome 15 deletion is Prader-Willi

P is for Paternal and Prader-Willi

Maternal Chromosome 15 deletion is Angelman

Mommy’s little angel

Note: due to imprinting, different genes would have been expressed by the paternal vs maternal regions, therefore it’s a net loss of different genes.

Question 14

Define pleiotropy

Answer 14

Individuals with the same genotype having different phenotypes.

Question 15

Define Proband

Answer 15

The first person in a pedigree to have a disease / trait.

Question 16

What is the recurrent risk for an autosomal dominant disease?

How would you identify it on a pedigree? (3)

What example of this was given?

Answer 16

50%

Equal in males and females, present in every generation, and an unaffected person can not transmit the disease.

Postaxial Polydactyly

Question 17

What is the recurrent risk for an autosomal recessive disease, if both parents are carriers?

How would you identify it on a pedigree? (3)

What example of this was given?

What special consideration increases risk?

Answer 17

25%

Unaffected parents can transmit the disease, skips generations, affects females and males equally.

Tyrosinase negative albinism

Consanguinity (First cousins mating)

Question 18

What is the transmission pathway for X-linked recessive?

How would you identify it on a pedigree? (3)

What example of this was given?

Answer 18

Female carriers transmit the disease allele to 50% of sons and daughters both. The sons are affected. An affected male will pass the allele to all of his children.

Half of female offspring of a carrier will be carriers. No females will be affected - except in crazy rare cases where an affected male mates with a carrier female.

Duchenne’s Muscular Dystrophy

Question 19

What is the pattern of recurrance for X-Linked Dominant Disease?

How would you identify it on a pedigree? (3)

What example of this was given?

Answer 19

Males pass the disease on 100% of the time to female children, and 0% to male children. Females pass the disease on 50% of the time.

Using the above information. Practically everyone is affected.

Hypophosphatemia

Question 20

What example was given for reduced penetrance?

Answer 20

Retinoblastoma

Question 21

What example was given for variable expressivity?

Answer 21

Neurofibromatosis

Question 22

What example was given for Locus Heterogeneity?

Answer 22

Osteogenesis Imperfecta

Question 23

If you have a mutation for a mitochondrial disease, you might still not present symptoms. What has to be reached before symptoms present?

Answer 23

The disease threshold.

Question 24

What is the example given for multifactorial inheritance?

Is it more common in women or men?

Is it more likely to be transmitted by a woman or a man?

Answer 24

Pyloric Stenosis

5x more common in men (Women have a higher risk threshold)

Women are more likely to pass it on. (“The recurrance risk is higher if the proband is a member of the less affected sex.”)