Chapter 7

Question 1

sex chromosome abnormality (SCA)

Answer 1

Any change from the normal number of sex chromosomes is a sex chromosome abnormality (SCA) regardless of whether the phenotype is affected.

Question 2

Trisomy X
47, XXX

Answer 2

-Common
-Normal physical phenotype, ind. is fertile (most likely due to inactivation of 2 of the Xs)
-Taller on average than other family members
-Slight delays in language and motor skills as well as higher incidence of social anxiety (however ultimate psychological and physical development cannot be predicted.)

Question 3

Tetrasomy X
48, XXXX

Answer 3

-rare
-associated w/ phenotype abnormalities
-females usually tall and have significant reductions in cognitive function and IQ
-small head, epicanthic folds and depressed nasal bridge
-incidence of skeletal abnormalities and unstable behavior is increased

Question 4

Pentasomy
49, XXXXX

Answer 4

-very rare
-fewer than 40 reported cases
-Among these individuals, consistent phenotypic features include severely reduced intellectual function, short stature, cleft palate, hypotonia, coarse facial features, microcephaly, hyperrelorism, and congenital heart defects.

Question 5

Klinefelter syndrome.
47, XXY

Answer 5

-male w/ extra X chromosome
-most commonly diagnosed SCA among males
-cause: both maternal and paternal nondisjunction
-associated with both maternal and paternal aging
-no morphological features at birth
- As the teen ages and becomes a young adult, testosterone levelsdecline and gonadotrophin hormone (luteinizing hormone [LH] and follicle-stimulating hormone (FSH]) levels become very high. Genitalia fail to grow, resulting in smaller testes and a smaller penis compared to those of normal peers. Gynecomastia (breast development in males) occurs in about 50% of individuals. Fertility problems include lack of sperm production {azoospermia) or greatly reduced sperm production (oligospermia) and decreased libido.
- Importantly, the ultimate potential of any affected person for completely normal physical and psychosocial development or for less than fully normal development cannot be predicted.

Question 6

Extra Y chromosome
47, XYY

Answer 6

-not sociales w/ phenotypic abnormalities
- occurs as an error in meiosis II of spermatogenesis. This is not an age-related problem.
-tall stature
-fertile

Question 7

Monosomy

Answer 7

-most likely occurs because of nondisjunction during meiosis for gamete formation.
-The only common incidence of monosomy among Living people is Turner syndrome, in which a female is missing one of the X chromosomes and has a karyotype of 45,X.

Question 8

Turner syndrome
45,X

Answer 8

-common, but 99% do not survive first trimester
-Girls with Turner syndrome are often, but not always, identified at birth (or even during pregnancy by ultrasound) because of the presence of “classic” phenotypic features.
-These include a smaller-than-expected size at full-term pregnancy, neck webbing, pedal edema, and cardiac abnormalities
-short stature, decreased childhood growth rate w/ no adolescent growth spurt
-ultimate psychological and iq potential cannot be predicted

Question 9

Common Features Associated With Turner Syndrome (45.X)
Table 7-1

Question 10

GENOTYPE-PHENOTYPE GENDER MISMATCH
Sex-reversal

Answer 10

-both phenotypic women with a 46,XY karyotype and phenotypic men with a 46,XX karyotype exist
-Early embryonic tissue capable of developing into male sex organs, including the penis, scrotum, prostate, and the tubular system connecting the testis to the urinary system, is the mesonephric ductal tissue (Wolffian glands). The tissue capable of developing into female sex organs is the pararnesonephric ductal tissue (Mullerian ducts). The mesonephric tissues have androgen (testosterone is one androgen) receptors on them, and the paramesonephric tissues do not. Interestingly, the gene coding for the androgen receptor (AR gene) is located on the X chromosome, which is nor where you would expect to find a gene for a male hormone receptOr.

Question 11

bipotential gonad,

Answer 11

at one time known as the indifferent gonad, has the potential to develop into a testis or an ovary, depending on which hormones and other factors influence it.

Question 12

androgen insesitivity syndrome (AIS)
XY females

Answer 12

-An identified genetic problem resulting in an XY genotype with a female phenotype is complete androgen insensitivity

Question 13

XX Males

Answer 13

-most common cause of this phenomenon is translocation of the SRY gene onto one of the X chromosomes
-men with this genotype share many characteristics with men who have Klinefelter
syndrome.

Question 14

Fragile X syndrome (FXS)
Martin-Bell syndrome, X-linked mental retardation, and macroorcbidism

Answer 14

-resulting from reduced or absent expression of the FMRJ (fragileX mental retardation 1) gene
-X-linked dominant with differences in severity related to differences in the number of repeat sequences, differences in penetrance, and random X-inactivation in different tissues.
-The protein coded by FMR1 is critical in brain development and maintenance of neural synapses. In classic FXS, the FMR1 gene-coding regions are normal, but the gene’s expression is silenced by large numbers of the trinucleotide sequence of CGG being repeated within the noncoding regions of the gene
-The term “fragile X” comes from the tendency of the X chromosome to exhibit a small break or gap at the end of the long arm

Question 15

Anticipation

Answer 15

-term used to describe that the phenotype of a genetic condition is expressed with greater severity and at earlier ages with successive generations.

Question 16

Expansion

Answer 16

-an increase, usually of trinucleotide repeat sequences, within a gene.
-For FXS, expansion of the CGG trinucleotide repeat sequences occurs with successive generations, leading to anticipation.
-The greatly expanded CGG regions increase the methylation of the FMR1 gene, silencing its expression and leading to the manifestations of classic FXS
-When the expansion results in 50 to 200 trinucleotide repeat sequences, the daughter has a premutation.
-The larger the number of expansions in a woman who has a premutation in her gametes, the more likely the expansions will continue within some gametes to progress to a full mutation (more than 200 trinucleotide repeat sequences) that, with fertilization, can result in offspring who do express FXS.
-All mothers of affected sons are carriers who have a 50% risk of transmitting the mutation with each pregnancy
-any woman who has the expansion has a 50% chance of transmitting the full mutation to her offipring with each pregnancy.

Question 17

Common Features Associated With Fragile X Syndrome
Table 7-2

Question 18

premutation

Answer 18

-People who have 55 to 200 repeats are said to have a “premutation” in the FMR1 gene. They do not have FXS but they might have, or may later develop, other fragile X-associated disorders.
-The difference in expression of this disorder in females who inherit the expansions is most likely the result of random X-inactivation (see Chapter 4). However, any woman who has the expansion has a 50% chance of transmitting the full mutation to her offipring with each pregnancy.

Question 19

oxidative phosphorylation

Answer 19

-Efficiently generates large amounts of ATP without the buildup of toxic wastes
-This reaction occurs within the mitochondria and requires sufficient amounts of oxygen and hydrogen molecules that have been stripped from our foodstuffs, especially sugar.

Question 20

Replication segregation

Answer 20

-the random sorting of newly synthesized mirochondria to new daughter cells
-As mtDNA within that single mitochondrion
replicates, that mirochondrion eventually has multiple
copies of mtDNA with the mutation along with mul-
tiple copies of normal mtDNA.

Question 21

Homoplasmy

Answer 21

When one daughter cell’s cytoplasm contains mitochondria with either all normal mtDNA or all mutated mtDNA,

Question 22

Heteroplasmy

Answer 22

When one daughter cell’s cytoplasm contains a mixture of mitochondria that have normal mtONA and mutated mtDNA,

Question 23

Summary

Answer 23

-Sex chromosome abnormalities (SCAs) of number occur much more frequently among live-born humans than do autosomal chromosome abnormalities, particularly of the X chromosome.
-Females who have an extra X chromosome and males who have an extra Y chromosome usually are undiagnosed because they do not have one or more obvious phenotypical differences compared with individuals whose sex chromosome numbers are completely normal.
-In addition, such individuals have normal fertility. Some of the earlier observations of individuals with SCA resulted in erroneous assumptions regarding intellectual ability, social behavior, and physical function.

Question 24

Summary part 2

Answer 24

• The most common sex chromosomal abnormality conceived is monosomy X (Turner syndrome, 45,X).
• Individuals with an extra X chromosome or an exrra Y chromosome are usually taller than other family
members.
• Unlike with autosornes, monosomy of a sex chromosome is compatible with life.
• With any sex chromosome disorder, the variation in expression is great, and the limitations or ultimate
potential of anyone affected person cannot be generalized or predicted.
• Early tissues that are capable of developing inro anatomical male sex structures (mesonephric ducts)
and those that are capable of developing into anaromical female sex structures (paramesonephric ducts)
are present in both XX and XY embryos.
• The most common mechanism for XY females is complete androgen insensitivity.
• The most common mechanism for XX males is translocation of the SRY gene to an X chromosome
during crossover in gametogenesis.
• Fragile X syndrome is the most common chromosomal disorder leading to reduced cognitive function
and decreased intellectual capacity in males.
• Fragile X prernurations can be expanded to full mutations in the ova of female carriers.
• Males do not inherit fragile X from their affected fathers.

Question 25

1. Which chromosomal trisomy is most often conceived?
   a. Trisomy 13
   b. Trisomy 18
   c. Trisomy 21
   d. Trisomy X

Answer 25

D

Question 26

2. Which genetic disorder is associated with older parental age at conception?
   a. 47,XYY
   b. Turner syndrome
   c. Klinefelter syndrome
   d. All mitochondrial disorders

Answer 26

C

Question 27

3. What mechanism is the most probable reason that females with a 47,XXX karyotype usually have a normal phenotype?
   a. 50% mosaicism for the extra X chromosome
   b. Consistent inactivation of two of the three X chromosomes
   c. Failure of chromosome segregation during meiosis II of gametogenesis
   d. Excessive methylation of genes on the paternally derived X chromosome

Answer 27

B

Question 28

4. Which health problems are common to both Turner and Klinefelter syndromes? Select all that apply.
   a. Sociopathic behavior
   b. Male-pattern baldness
   c. Germ cell tumors
   d. Color blindness
   e. Osteoporosis
   f. Infertility

Answer 28

C, e, f

Question 29

5. Why does injection of testosterone fail to induce male secondary sex characteristics in females who are 46,XY with complete androgen insensitivity?
   a. Their target tissues for testosterone lack testosterone receptors.
   b. The injected testosterone is destroyed just as rapidly as their own naturally produced testosterone.
   c. Their production of estrogen far exceeds the amount of testosterone that can be administered safely.
   d. The injected testosterone inhibits the gonadotrophin hormone feedback loops, decreasing the
   production of testosterone by the remaining testicular tissue.

Answer 29

A

Question 30

6. Which situation or condition best exemplifies anticipation?
   a. Expression of the disorder is the same for dizygotic twins as it is for monozygotic twins.
   b. A mother of a child with a mitochondrial disorder elects to have surgical sterilization.
   c. Clinical manifestations of a disorder become less severe or noticeable as the person ages.
   d. A son with a genetic problem expresses symptoms 20 years earlier than his mother did.

Answer 30

D

Question 31

7. A 39-year-old man with mitochondrial disease is in profound heart failure. What is the source of the heart failure?
   a. Structural malformation of the heart muscle from mitochondrial mutations.
   b. Structural malformation of the major heart valves from mitochondrial mutations.
   c. Failure of the heart muscle cells to contract effectively because of decreased cellular energy production.
   d. Failure of the aortic and pulmonic valves to close effectively because of decreased cellular energy
   production.

Answer 31

C

Question 32

S. A 21-year-old soldier disappeared in Vietnam. Forty years later, bones are discovered that may include his remains. Which available living relative’s mitochondrial DNA would provide the most accurate comparison sample to determine whether the bones belong to this soldier?
a. Father
b. Daughter
c. Sister’s son
d. Brother’s daughter

Answer 32

C

Question 33

9. Which molecular mechanism is responsible for the phenotype of fragile X syndrome?
   a. Failure of the X chromosome to undergo correct segregation during meiosis II of gametogenesis.
   b. Presence of excessive trinucleotide repeat sequences in the noncoding regions of the FMRI gene.
   c. Premature “splicing out” of the AGG47 I intron during early translation of the FMRI gene.
   d. Whole body absence of receptors for the FMRI gene product.

Answer 33

B

Question 34

Adam had one daughter (Beverly) when he was 25 years old, another (Bonnie) when he was 27 years old, and a son (Brian) when he was 30. Bonnie has two sons and a daughter. Her first son (Charlie) has many developmental delays, and the pediatrician has done enzyme studies for specific biochemical disorders. All were negative. When Charlie is 6 years old, his maternal aunt (Adam’s first daughter, Beverly) is 40 years old and pregnant. As part of prenatal diagnostic work, she has blood drawn for genetic disorders, and an amniocentesis is performed. The amniocentesis indicates she is pregnant with a normal girl. However, Beverly’s blood work reveals that she is a fragile X syndrome premutation carrier. When Beverly tells Bonnie about this, Bonnie informs her pediatrician about Beverly’s premutation carrier status. The pediatrician sends Charlie for testing, and he is found to have more than 1,000 CGG trinucleotide repeat sequences in his FMR1 gene alleles with 90% methylation, giving him a diagnosis of fragile X syndrome.
1. What risks do Bonnie’s children have for premutation carrier status?
2. What risks do Beverly’s children have for premutation carrier status or for FXS?
3. What risks do Brian’s children have for premutation carrier status or for FXS?
4. Why is Adam unaffected?
5. What are the risks for Adam’s mutation status to change to a full mutation? Explain your response.