ESSENTIALS OF PATHOPHYSIOLOGY CHAPTER 6 GENETIC AND CONGENITAL DISORDERS

PRE LECTURE QUIZ

(TRUE/FALSE) T F F T F      Most genetic disorders are caused by an alteration in the deoxyribonucleic acid (DNA) sequence that alters the synthesis of a single gene product.

Autosomal recessive disorders are manifested even if only one member of the gene pair is affected.

A teratogenic agent is an environmental agent that produces abnormalities only during the first 4 weeks of embryonic or fetal development.

Down syndrome, Turner syndrome, and Klinefelter syndrome are all examples of chromosomal disorders that occur from an alteration in chromosome number.

Cleft lip and palate is an example of an autosomal dominant disorder.

PRE LECTURE QUIZ

Neurofibromatosis

 Autosomal dominant disorders involve a ______________ mutant allele that is transmitted from an affected parent to an offspring.

Single Folic

  Sex-linked disorders almost always are associated with the __________ chromosome and are predominantly recessive.

An individual with ______________ syndrome would be female, short in stature, and lacking in breast development, and would not menstruate.

Turner X

  _____________________, an autosomal dominant disorder, is a condition involving neurogenic tumors that arise from Schwann cells and other elements of the peripheral nervous system.

Neural tube defects are often the result of ______________ acid deficiency.

GENES ARE FOUND ON CHROMOSOMES

 X or Y chromosome: sex-linked  Other chromosomes: autosomal

Female Male Without Trait Tree Structure With Trait

Autosomal Recessive Trait Carriers, Diseased and non Diseased

Sex Linked showing Female Carriers

ALLELES

 Alleles are copies of a gene  If all your copies of a gene are alike, you are homozygous  If they differ, you’re heterozygous  If you are heterozygous for a recessive trait and do not show it, you are a carrier  If you have only one copy of a gene, you are hemizygous

QUESTION

Which of the following statements is true about an individual who is a carrier for the cystic fibrosis (CF) gene?

a.

Homozygous; suffers from CF b.

Homozygous; does not suffer from CF c.

d.

Heterozygous; suffers from CF Heterozygous; does not suffer from CF

ANSWER

d.

Heterozygous; does not suffer from CF If an individual is a carrier, they are heterozygous for the recessive trait (in this case, CF), but they do not display the trait (because the trait is recessive).

DISCUSSION:

If you have the allele for a trait, do you display the trait?

 No: It is recessive  Yes: It is dominant  Sometimes: It has intermediate penetrance

SCENARIO:

A Young Man’s Father Died of Brugada  Unexplained sudden death   Syndrome … Due to mutation in the gene from the Na+ channel in cardiac muscle Autosomal dominant trait   His mother is alive and healthy Both grandmothers are alive and healthy Question: What is the son’s chance of having the disease?

PUNNETT SQUARE: SINGLE-GENE AUTOSOMAL

Dad’s alleles Mom’s alleles b b b b b b b B B b B b

PENETRANCE

 Brugada syndrome has only a 12.5% penetrance  What does this mean for the young man whose father died of it?

SEX-LINKED TRAITS

 The gene is usually on the X chromosome  If Brugada syndrome were sex-linked, what would the young man’s father’s genotype have been?

 What would his chances of inheriting the disease be?

QUESTION

If an unaffected mother carries one normal and one mutant allele on her X chromosome, what are the chances that she will transmit the defective gene to her sons?

a.

25% b.

c.

d.

50% 75% 100%

ANSWER

b.

50% Because a son receives the X sex chromosome from his mother (who has one normal and one mutant allele), there is a 50% chance that the mutant allele will be inherited.

PUNNETT SQUARE: SINGLE-GENE SEX-LINKED

Mom’s alleles Dad’s alleles X b X b Y X b Y X b Y X B X b X B X b X B

MITOCHONDRIAL DNA

 Codes for the proteins needed for aerobic metabolism  Mitochondria all come from the mother  She has many more than two mitochondria, so she may pass several different mitochondrial alleles to the child (Mendelian Inheritance in Man. [2005].

Mitochondrial deafness modifier gene

. Retrieved May 15, 2005, from http://www.ncbi.nlm.nih.gov/entrez/ dispomim.cgi?cmd=entry&id=221745 .)

CHROMOSOMAL DAMAGE

 Breakage and rearrangement  Deletion  Inversion  Isochromosome formation  Ring formation  Translocation

QUESTION

Which type of chromosome alteration generally results in normal offspring?

a.

Deletion b.

c.

d.

Inversion Translocation Ring formation

ANSWER

c.

Translocation Translocation is the only chromosomal alteration where no genetic material is actually lost (chromosome parts are exchanged), so the offspring are usually normal. Offspring are translocation carriers, so their children may or may not be normal.

ALTERATIONS IN CHROMOSOME DUPLICATION

 Mosaicism  Aneuploidy  Monosomy  Polysomy  Trisomy º Down syndrome

Klinefelter’s Syndrome

ENVIRONMENTAL CAUSES FOR CONGENITAL DISORDERS

Scenario: Mrs. K is a diabetic and is having trouble keeping her blood glucose constant during pregnancy…  She works in a dry-cleaners store next to a gas station and drinks heavily.

 She is diagnosed with toxoplasmosis.

Question: What kinds of stresses is her fetus experiencing?