Most major metabolic pathways are considered to be either mainly anabolic or catabolic. Which of the following pathways is most correctly considered to be amphibolic?
A. Lipolysis
B. Glycolysis
C. Oxidation of fatty acids
D. Citric acid cycle
E. Gluconeogenesis
2.
If a homogenate of liver cells is centrifuged to remove all cell membranes and organelles, which of the following enzyme activities will remain in the homogenate?
A. Glucose-6-phosphate dehydrogenase
B. Glycogen synthetase
C. Aconitase
D. Acyl CoA hydratase
E. Hydroxybutyrate dehydrogenase
3.
Which of the following is appropriate for a patient with renal failure?
A. High-carbohydrate diet
B. High-protein diet
C. Low-fat diet
D. High-fiber diet
E. Free water of at least 3 L per day
4.
An adolescent presents with abdominal discomfort, abdominal fullness, excess gas, and weight loss. Blood glucose, cholesterol, and alkaline phosphatase levels are normal. There is no jaundice or elevations. The stool tests positive for reducing substances. Which of the following is the most likely diagnosis?
A. Diabetes mellitus
B. Starvation
C. Nontropical sprue
D. Milk intolerance
E. Gallstones
5.
Juvenile diabetes mellitus is a disorder of carbohydrate metabolism caused by insulin deficiency. The disease often follows a viral infection with inflammation of the pancreatic cells, but also exhibits genetic predisposition with a 40 to 50% concordance rate in monozygous twins and clustering in families. Juvenile diabetes mellitus is best described as what type of disorder?’
A. Congenital disorder
B. Multifactorial disorder
C. Mendelian disorder
D. Sporadic disorder
E. Sex-limited disorder
6.
A couple is referred to the physician because their first three pregnancies have ended in spontaneous abortion. Chromosomal analysis reveals that the wife has two cell lines in her blood, one with a missing X chromosome (45,X) and the other normal (46,XX). Which of the following is the best description of her chromosomal constitution?
A. Chimeric
B. Monoploid
C. Trisomic
D. Mosaic
E. Euploid
7.
A child with cleft palate, a heart defect, and extra fifth fingers is found to have 46 chromosomes with extra material on one homologue of the chromosome 5 pair. This chromosomal abnormality is best described by which of the following terms?
A. Polyploidy
B. Balanced rearrangement
C. Ring formation
D. Mosaicism
E. Unbalanced rearrangement
8.
A 10-year-old boy is referred to the physician because of learning problems and a lack of motivation in school. His family history is unremarkable. Physical examination is normal except for single palmar creases of the hands and curved fifth fingers (clinodactyly). The physician decides to order a karyotype. Which of the following indications for obtaining a karyotype would best explain the physician's decision in this case?
A. A couple with multiple miscarriages, or a person who is at risk for an inherited chromosome rearrangement
B. A child with ambiguous genitalia who needs genetic sex assignment
C. A child with an appearance suggestive of Down's syndrome or other chromosomal disorder
D. A child with mental retardation and/or multiple congenital anomalies
E. A child who is at risk for
9.
Chromosomal analysis reveals a 47,XYY karyotype. Which of the following descriptions best fits this abnormality?
A. Autosomal trisomy
B. A male with Klinefelter's syndrome
C. Sex chromosome aneuploidy
D. A female with Turner's syndrome
E. Sex chromosome triploidy
10.
Which of the following karyotypes is an example of aneuploidy?
A. 46,XX
B. 23,X
C. 69,XXX
D. 92,XXXX
E. 90,XX
11.
Which of the following is the proper cytogenetic notation for a female with Down's syndrome mosaicism?
A. 46,XX,+21/46,XY
B. 47,XY,+21
C. 47,XXX/46,XX
D. 47,XX,+21/46,XX
E. 47,XX,+21(46,XX)
12.
A newborn girl is found to have marked swelling of the dorsal areas of her feet along with a broad (webbed) neck, a broad chest, and a heart murmur that is due to coarctation of the aorta. Her physician suspects a chromosomal disorder and orders a karyotype. Which of the results pictured below is most likely?
B. Result B
C. Result C
D. Result D
13.
A 2-week-old baby is hospitalized for inadequate feeding and poor growth. The parents are concerned by the child's weak cry. An experienced grandmother accompanies them, saying she thought the cry sounded like a cat's meow. The grandmother also states that the baby doesn't look much like either parent. The physician orders a karyotype after noting a small head size (microcephaly) and subtle abnormalities of the face. Which of the results pictured below is most likely?
B. Result B
C. Result C
D. Result D
E. Result E
14.
A child with cleft palate, a heart defect, and extra fifth fingers is found to have 46 chromosomes with extra material on one homologue of the chromosome 5 pair. This chromosomal abnormality is best described by which of the following terms?
A.Polyploidy
B.Balanced rearrangement
C.Ring formation
D.Mosaicism
E.Unbalanced rearrangement
15.
A 10-year-old boy is referred to the physician because of learning problems and a lack of motivation in school. His family history is unremarkable. Physical examination is normal except for single palmar creases of the hands and curved fifth fingers (clinodactyly). The physician decides to order a karyotype. Which of the following indications for obtaining a karyotype would best explain the physician's decision in this case?
A. A couple with multiple miscarriages, or a person who is at risk for an inherited chromosome rearrangement
B. A child with ambiguous genitalia who needs genetic sex assignment
C. A child with an appearance suggestive of Down's syndrome or other chromosomal disorder
D. A child with mental retardation and/or multiple congenital anomalies
E. A child who is at risk for cancer
16.
Chromosomal analysis reveals a 47,XYY karyotype. Which of the following descriptions best fits this abnormality?
A.Autosomal trisomy
B.A male with Klinefelter's syndrome
C.Sex chromosome aneuploidy
D.A female with Turner's syndrome
E.Sex chromosome triploidy
17.
Which of the following karyotypes is an example of aneuploidy?
A.46,XX
B.23,X
C.69,XXX
D.92,XXXX
E.90,XX
18.
Which of the following is the proper cytogenetic notation for a female with Down's syndrome mosaicism?
A.46,XX,+21/46,XY
B.47,XY,+21
C.47,XXX/46,XX
D.47,XX,+21/46,XX
E.47,XX,+21(46,XX)
19.
Gardner's syndrome is an autosomal dominant condition characterized by multiple polyps of the intestines, bony tumors, skin cysts, and a high risk of intestinal cancer. A family is encountered in which a great-grandfather, grandmother, and father are affected with Gardner's syndrome and develop intestinal cancer in their thirties. The father brags that none of his four children have inherited Gardner's syndrome because they lack skin cysts and have not had cancer. The chance that at least one child has inherited the Gardner's syndrome allele, and the reason the children have not manifested cancer, are
A.1/4, ascertainment bias
B.1/2, variable cancer predisposition
C.3/4, early-onset disease manifestation
D.13/16, incomplete medical evaluation
E.15/16, later-onset disease manifestation
20.
Ectrodactyly is an autosomal dominant trait that causes missing middle fingers (lobster claw malformation). A grandfather and grandson both have ectrodactyly, but the intervening father has normal hands by x-ray. Which of the following terms applies to this family?
A.Incomplete penetrance
B.New mutation
C.Variable expressivity
D.Germinal mosaicism
E.Anticipation
ANSWERS
In general, the corresponding pathways of catabolism and anabolism are not identical (glycolysis versus gluconeogenesis, lipolysis and oxidation of fatty acids versus fatty acid synthesis and lipogenesis, glycogenolysis versus glycogenesis). However, the citric acid cycle is a central pathway from which anabolic precursors of biosynthetic reactions may derive or into which the complete catabolism of small molecules to carbon dioxide and water may occur. For these reasons, the citric acid cycle is often called an amphibolic pathway.
2. A
Centrifugation of a cellular homogenate at a force of 100,000 × g will pellet all cellular organelles and membranes. Only soluble cellular molecules found in the cytosol will remain in the supernatant. Thus, the enzymes of glycolysis and most of those of gluconeogenesis, fatty acid synthesis, and the pentose phosphate pathway will be in the supernatant. Glucose-6-phosphate dehydrogenase, which results in the formation of 6-phosphoglucono- -lactone from glucose-6-phosphate, is the committed step in the pentose phosphate pathway. In the pellet will be the enzymes within mitochondria, including those of the citric acid cycle (aconitase), fatty acid oxidation (acyl CoA hydratase), and ketogenesis (hydroxybutyrate dehydrogenase). Enzymes of glycogen degradation and synthesis (glycogen synthetase) will also be in the pellet associated with glycogen particles.
3. A
A diet high in carbohydrate and fats spares glucose use and inhibits gluconeogenesis, thereby preventing protein catabolism and nitrogen production. A major function of the kidneys is to excrete nitrogen catabolized from proteins in the form of urea. Indeed, the major clinical measures of renal function are products of protein catabolism [blood urea nitrogen (BUN) and blood creatinine]. A diet for a patient with renal failure should therefore minimize protein and nitrogen load. Although 3 L/day of fluid is a normal intake for adults with healthy kidneys, glomerular filtration and water excretion are decreased in renal failure. Water and salt intake (particularly potassium) must therefore be limited in renal failure. Excess water or salt intake in patients with renal disease is manifest clinically by edema (swollen eyelids, swollen lower limbs).
4. D
Milk intolerance may be due to milk protein allergies during infancy, but it is commonly caused by lactase deficiency in older individuals. Intestinal lactase hydrolyzes the milk sugar lactose into galactose and glucose, both reducing sugars that can be detected as reducing substances in the stool. The symptoms of lactose intolerance (lactase deficiency) and other conditions involving intestinal malabsorption include diarrhea, cramps, and flatulence due to water retention and bacterial action in the gut. In nontropical sprue, symptoms seem to result from the production of antibodies in the blood against fragments of wheat gluten. It seems likely that a defect in intestinal epithelial cells allows tryptic peptides from the digestion of gluten to be absorbed into the blood, as well as to exert a harmful effect on intestinal epithelia.
Gallbladder inflammation (cholecystitis) usually presents with acute abdominal pain (colic) with radiation to the right shoulder. The normal composition of bile is about 5% cholesterol, 15% phosphatidylcholine, and 80% bile salt in a micellar liquid form. Increased cholesterol from high-fat diets or genetic conditions can upset the delicate micellar balance, leading to supersaturated cholesterol or cholesterol precipitates that cause gallstone formation. Removal of the gallbladder is a common treatment for this painful condition.
Mobilization of fats with the production of ketone bodies occurs during fasting and starvation, but ketone production is well controlled. During uncontrolled diabetes mellitus, ketogenesis proceeds at a rate that exceeds the buffering capacity of the blood to produce ketoacidosis.
5. B
Many common diseases are caused by a combination of environmental and genetic factors, and are described as multifactorial diseases. Examples include diabetes mellitus, schizophrenia, alcoholism, and many common birth defects such as cleft palate or congenital dislocation of the hip. The proportion of genetically identical monozygous twins who share a trait such as diabetes mellitus provides a measure of the genetic contribution to etiology (hereditability). Mendelian disorders are completely determined by the genotype of an individual, and exhibit 100% concordance in identical twins. Sporadic disorders have no genetic predisposition and do not cluster in families except by chance or through similar environmental exposure. Congenital disorders are present at birth, in contrast to juvenile diabetes mellitus, which usually presents during childhood. Sex-limited disorders occur predominantly in males or females, in contrast to the approximately equal sex distribution of juvenile diabetes mellitus.
6. D
The case described represents one of the more common chromosomal causes of reproductive failure, Turner mosaicism. Turner's syndrome represents a pattern of anomalies including short stature, heart defects, and infertility. Turner's syndrome is often associated with a 45,X karyotype (monosomy X) in females, but mosaicism (i.e., two or more cell lines with different karyotypes in the same individual) is common. However, chimerism (i.e., two cell lines in an individual arising from different zygotes, such as fraternal twins who do not separate) is extremely rare. Trisomy refers to three copies of one chromosome, euploidy to a normal chromosome number, and monoploidy to one set of chromosomes (haploidy in humans).
7. E
Chromosomal abnormalities may involve changes in number (i.e., polyploidy and aneuploidy) or changes in structure (i.e., rearrangements such as translocations, rings, and inversions). Extra material (i.e., extra chromatin) seen on chromosome 5 implies recombination of chromosome 5 DNA with that of another chromosome to produce a rearranged chromosome. Since this rearranged chromosome 5 takes the place of a normal chromosome 5, there is no change in number of the autosomes (nonsex chromosomes) or sex chromosomes (X and Y chromosomes). The question implies that all cells karyotyped from the patient (usually 11 to 25 cells) have the same chromosomal constitution, ruling out mosaicism. The patient's clinical findings are similar to those occurring in trisomy 13, suggesting that the extra material on chromosome 5 is derived from chromosome 13, producing an unbalanced karyotype called dup(13) or partial trisomy 13.
8. D
The hallmarks of children with chromosomal anomalies are mental retardation and multiple congenital anomalies. In this case, the individual has learning problems that have not yet been recognized as mental retardation, and he has minor anomalies rather than major birth defects that cause cosmetic or surgical problems. The physician was astute to suspect a chromosomal anomaly even when the developmental disability and alterations in physical appearance were subtle. Other indications for a karyotype include a couple with multiple miscarriages, an individual at risk for inheriting or transmitting a chromosomal rearrangement, a child with ambiguous external genitalia, or an individual with characteristics of a chromosomal syndrome such as Down's, Turner's, or Klinefelter's syndrome. Chromosome translocations are characteristic of many types of cancer, but these occur in somatic cancer cells rather than in the patient's germ line.
9. C
The 47,XYY karyotype is an example of sex chromosome aneuploidy, as are Klinefelter's syndrome (47,XXY), Turner's syndrome (45,X), and triple X syndrome (47,XXX). Sex chromosome mixoploidy implies mosaicism, such as 45,X/46,XX with two cell lines in one individual. Autosomal trisomies include Down's syndrome [47,XX+21 (trisomy 21)], Patau's syndrome [47,XX+13 (trisomy 13)], and Edwards' syndrome [47,XY+18 (trisomy 18)].
10. E
Aneuploidy involves extra or missing chromosomes that do not arise as increments of the haploid chromosome number n. Polyploidy involves multiples of n, such as triploidy (3n = 69,XXX) or tetraploidy (4n = 92,XXXX). Diploidy (46,XX) and haploidy (23,X) are normal karyotypes in gametes and somatic cells, respectively. A 90,XX karyotype represents tetraploidy with two missing X chromosomes, which has been seen in one patient who had features that resembled those of Turner's syndrome.
11. D
Mosaicism occurs when a chromosomal anomaly affects one of several precursor cells of an embryo or tissue. The two or more karyotypes that characterize the mosaic cells are separated by a slash in cytogenetic notation. The notation 47,XX,+21 denotes a cell line typical of a female with trisomy 21 (Down's syndrome), while 46,XX is the karyotype expected for a normal female.
12. A
A chromosome study or karyotype delineates the number and kinds of chromosomes in one cell karyon (nucleus). Blood is conveniently sampled, so most chromosomal studies or karyotypes are performed on peripheral leukocytes in blood. A number of leukocytes are karyotyped under the microscope (10 to 25, depending on the laboratory), and a representative photograph is taken. The chromosome images are then arranged (cut out by hand or moved by computer) in order of size from the #1 pair to the #22 pair, and this ordered array is also called a karyotype. Except in cases of mosaicism (different karyotypes in different tissues), the peripheral blood karyotype is indicative of the germ-line karyotype that is characteristic for an individual. In most cases of Turner's syndrome there is a lack of one X chromosome, as in panel A, which shows one X (arrow) and no Y chromosome. Other cases involve mosaicism (45,X/46,XX or 45,X/46,XY) or isochromosomes (e.g., 46,X,isoXq). Correlation of karyotypes and phenotypic features of girls with Turner's syndrome has demonstrated that haploinsufficiency (partial monosomy) of the short arm (Xp) is what generates the characteristic manifestations (web neck, shield chest, puffy feet, coarctation). Women with Turner's syndrome also have short stature and infertility due to maldevelopment of the ovaries (streak gonads).
13. E
Children with chromosome abnormalities often exhibit poor growth (failure to thrive) and developmental delay with an abnormal facial appearance. This baby is too young for developmental assessment, but the catlike cry should provoke suspicion of cri-du-chat syndrome. Cri-du-chat syndrome is caused by deletion of the terminal short arm of chromosome 5 [46,XX,del(5p), also abbreviated as 5p–] as depicted in panel e. When a partial deletion or duplication like this one is found, the parents must be karyotyped to determine if one carries a balanced reciprocal translocation. The other karyotypes show (a) deletion of the short arm of chromosome 4 [46,XY,del(4p) or 4p–]; (b) XYY syndrome (47,XYY); (c) deletion of the long arm of chromosome 13 [46,XX,del(13q) or 13q–]; (d) Klinefelter's syndrome (47,XXY). Most disorders involving excess or deficient chromosome material produce a characteristic and recognizable phenotype (e.g., Down's, cri-du-chat, or Turner's syndrome). The deletion of 4p– (panel A) produces a pattern of abnormalities (syndrome) known as Wolf-Hirschhorn syndrome; deletion of 13q– produces a 13q– syndrome (no eponym). The mechanism(s) by which imbalanced chromosome material produces a distinctive phenotype is completely unknown.
14. E
Chromosomal abnormalities may involve changes in number (i.e., polyploidy and aneuploidy) or changes in structure (i.e., rearrangements such as translocations, rings, and inversions). Extra material (i.e., extra chromatin) seen on chromosome 5 implies recombination of chromosome 5 DNA with that of another chromosome to produce a rearranged chromosome. Since this rearranged chromosome 5 takes the place of a normal chromosome 5, there is no change in number of the autosomes (nonsex chromosomes) or sex chromosomes (X and Y chromosomes). The question implies that all cells karyotyped from the patient (usually 11 to 25 cells) have the same chromosomal constitution, ruling out mosaicism. The patient's clinical findings are similar to those occurring in trisomy 13, suggesting that the extra material on chromosome 5 is derived from chromosome 13, producing an unbalanced karyotype called dup(13) or partial trisomy 13.
15. D
The hallmarks of children with chromosomal anomalies are mental retardation and multiple congenital anomalies. In this case, the individual has learning problems that have not yet been recognized as mental retardation, and he has minor anomalies rather than major birth defects that cause cosmetic or surgical problems. The physician was astute to suspect a chromosomal anomaly even when the developmental disability and alterations in physical appearance were subtle. Other indications for a karyotype include a couple with multiple miscarriages, an individual at risk for inheriting or transmitting a chromosomal rearrangement, a child with ambiguous external genitalia, or an individual with characteristics of a chromosomal syndrome such as Down's, Turner's, or Klinefelter's syndrome. Chromosome translocations are characteristic of many types of cancer, but these occur in somatic cancer cells rather than in the patient's germ line.
16. C
The 47,XYY karyotype is an example of sex chromosome aneuploidy, as are Klinefelter's syndrome (47,XXY), Turner's syndrome (45,X), and triple X syndrome (47,XXX). Sex chromosome mixoploidy implies mosaicism, such as 45,X/46,XX with two cell lines in one individual. Autosomal trisomies include Down's syndrome [47,XX+21 (trisomy 21)], Patau's syndrome [47,XX+13 (trisomy 13)], and Edwards' syndrome [47,XY+18 (trisomy 18)].
17. E
Aneuploidy involves extra or missing chromosomes that do not arise as increments of the haploid chromosome number n. Polyploidy involves multiples of n, such as triploidy (3n = 69,XXX) or tetraploidy (4n = 92,XXXX). Diploidy (46,XX) and haploidy (23,X) are normal karyotypes in gametes and somatic cells, respectively. A 90,XX karyotype represents tetraploidy with two missing X chromosomes, which has been seen in one patient who had features that resembled those of Turner's syndrome.
18. D
Mosaicism occurs when a chromosomal anomaly affects one of several precursor cells of an embryo or tissue. The two or more karyotypes that characterize the mosaic cells are separated by a slash in cytogenetic notation. The notation 47,XX,+21 denotes a cell line typical of a female with trisomy 21 (Down's syndrome), while 46,XX is the karyotype expected for a normal female.
19. E
The father is affected with Gardner's syndrome (175100), an autosomal dominant disease. Therefore, each of his four children has a 1/2 chance of receiving the allele that causes Gardner's syndrome and a 1/2 chance of receiving the normal allele. The probability that none of his four children received the allele for Gardner's syndrome is thus the joint probability of four independent events, computed by the product 1/2 × 1/2 × 1/2 × 1/2 = 1/16. The probability that at least one child has received the abnormal Gardner's syndrome allele is thus 1 – 1/16 = 15/16. Gardner's syndrome is one of many genetic disorders that may not be obvious in early childhood. Intestinal cancer in particular has a later onset, with 50% of patients being affected by age 30 to 35. More extensive evaluation of the children for internal signs of disease (e.g., the bony tumors) is required before the father can conclude that he has not transmitted the gene. Late-onset disorders are an important category of adult genetic disease, and presymptomatic testing for these diseases is a novel application of DNA diagnosis.
20. A
Incomplete penetrance applies to a normal individual who is known from the pedigree to have an allele responsible for an autosomal dominant trait. Variable expressivity refers to family members who exhibit signs of the autosomal dominant disorder that vary in severity. When this severity seems to worsen with progressive generations, it is called anticipation. A new mutation in the grandson would be extremely unlikely given the affected grandfather. The father could be an example of somatic mosaicism if a back-mutation occurred to allow normal limb development, but there is no reason to suspect mosaicism of his germ cells (germinal mosaicism).
