1			True or False a. Mendel and Morgan and other pre-molecular geneticists equated a locus with a gene. b. With the advent of molecular genetics, any DNA site that is different among genomes is an allele. c. Microsatellites, compared to coding genes, show less variation. d. Restriction sites frequently undergo unequal crossing-over. e. Microsatellite analysis by PCR requires knowledge of the flanking sequence. f. The same hybridization probe can detect members of minisatellite families on different chromosomes.
			A)	TTTFTT
			B)	TTFTFT
			C)	TTFFTT
			D)	FTTTTF
			E)	TFTTTF
2			True or False a. The expanded CAG repeats in Huntington disease alleles disrupt the reading frame. b. The DNA fingerprints of monozygotic twins would be expected to be identical. c. A deletion always gives rise to a null mutation. d. PCR can be performed only on living tissue samples. e. Positional cloning requires knowledge about the function of a gene. f. Women with the BRCA1 allele invariably develop breast cancer.
			A)	FTFFFT
			B)	FTTTFF
			C)	FTFTTT
			D)	FTFFFF
			E)	FFFTTF
3			If the parents are heterozygous for a particular microsatellite locus, the chance of a child being heterozygous at that locus is:
			A)	1/1
			B)	1/3
			C)	1/4
			D)	1/2
			E)	0
4			If you sequence the 50 kb beta-globin locus from one chromosome, how many base sequence differences do you expect between that sequence and the same region in another individual? Need a Hint?
			A)	0
			B)	fewer than 10
			C)	50
			D)	150
			E)	more than 100
5			In minisatellites, _____________ base sequences are tandemly repeated about _______ times: Need a Hint?
			A)	one to three; 15-100
			B)	20-100; 10-1000s
			C)	one to three; 10-1000s
			D)	20-100; 15-100
			E)	none of the above
6			In microsatellites, _____________ base sequences are tandemly repeated about _______ times: Need a Hint?
			A)	one to three; 15-100
			B)	20-100; 10-1000s
			C)	one to three; 10-1000s
			D)	20-100; 15-100
			E)	none of the above
7			Which of the following is the main source of variation in minisatellites? Need a Hint?
			A)	chemicals in water
			B)	chemicals in food
			C)	ultraviolet light
			D)	unequal crossing-over
			E)	faulty DNA replication
8			For linkage analysis, what variable most determines a marker's ability to predict genotype? Need a Hint?
			A)	presence on the X chromosome
			B)	map distance from allele
			C)	size of restriction fragment
			D)	size of disease gene
			E)	recognition sequence

(Questions 9-11)

Allele specific oligonucleotides (ASO) can be used to determine the different alleles present in a DNA sample. Single sperm (from a single donor), which have completed meiosis, can be used for a polymerase chain reaction (PCR). The amplified DNA is then spotted to filters and hybridized with probes that discriminate between single nucleotide substitutions. Four primers (called A, B, D, and E) were used to amplify DNA samples and ASO probes were used to determine the allele present, visualized as a black dot. For each locus, the left side of the filter is probed with one ASO (e.g. A1) and the right side is probed with the other one (e.g. A2).

<a onClick="window.open('/olcweb/cgi/pluginpop.cgi?it=gif:: ::/sites/dl/free/0072919302/56741/chap11mc_table_9_11.gif','popWin', 'width=343,height=344,resizable,scrollbars');" href="#"><img valign="absmiddle" height="16" width="16" border="0" src="/olcweb/styles/shared/linkicons/image.gif"> (5.0K)</a>

9			Which loci are heterozygous? Need a Hint?
			A)	D
			B)	B
			C)	A, C
			D)	A, C, E
			E)	A, C, E, B
10			Which loci are tightly linked? Need a Hint?
			A)	A & C
			B)	C & D
			C)	B & D
			D)	A & E
			E)	C & E
11			What might the data for allele B represent? Need a Hint?
			A)	an X-linked gene
			B)	a Y-linked gene
			C)	meiotic nondisjunction
			D)	a or b
			E)	b & c

(Questions 12 and 13)

Microsatellites are very useful as DNA markers. They consist of 1-3 bp units repeated 15-100 times in a row. They are highly polymorphic, with multiple alleles that differ in 2 or 3 bp unit increments. The multiple alleles can be detected as PCR products of different sizes. One particular microsatellite has four alleles in the population and is closely linked to an autosomal dominant form of early Alzheimer’s disease.

12			A pedigree and microsatellite analysis of a family with a history of early Alzheimer's is indicated below: <a onClick="window.open('/olcweb/cgi/pluginpop.cgi?it=gif:: ::/sites/dl/free/0072919302/56741/chap11mc_table_12.gif','popWin', 'width=395,height=354,resizable,scrollbars');" href="#"><img valign="absmiddle" height="16" width="16" border="0" src="/olcweb/styles/shared/linkicons/image.gif"> (3.0K)</a> Which polymorphism is early Alzheimer's associated with in this family? Does the male indicated by the ? carry the allele for early Alzheimer's? Need a Hint?
			A)	2; yes
			B)	2; no
			C)	3; no
			D)	1; no
			E)	2; can't tell
13			A pedigree and microsatellite analysis of a different family with a history of early Alzheimer's is indicated below: <a onClick="window.open('/olcweb/cgi/pluginpop.cgi?it=gif:: ::/sites/dl/free/0072919302/56741/chap11mc_table_13.gif','popWin', 'width=439,height=356,resizable,scrollbars');" href="#"><img valign="absmiddle" height="16" width="16" border="0" src="/olcweb/styles/shared/linkicons/image.gif"> (3.0K)</a> Which polymorphism is early Alzheimer's associated with in this family? Does the female indicated by the ? carry the allele for early Alzheimer's? Need a Hint?
			A)	1; yes
			B)	1; no
			C)	2; no
			D)	4; no
			E)	1; can't tell
14			Mapping a human disease gene requires: Need a Hint?
			A)	large pedigrees or large numbers of markers.
			B)	complete sequence of the chromosome.
			C)	antibodies to the protein in question.
			D)	knowledge of the mutant sequence.
			E)	an animal model.
15			Which of the steps listed below is not involved in Northern analysis? Need a Hint?
			A)	Blot the RNA from the gel to a filter
			B)	Purify the RNA
			C)	Separate the RNA by size in an electrical field in an agarose gel
			D)	Expose the filter to a labeled probe to allow hybridization
			E)	Make cDNA using reverse transcriptase
16			A transgene: Need a Hint?
			A)	can be used to create new mutant organisms.
			B)	is foreign DNA added to a genome.
			C)	can reverse a disease phenotype.
			D)	a, b and c
			E)	a and c
17			Incomplete penetrance: Need a Hint?
			A)	underlies human height variation.
			B)	is observed when the mutant genotype does not result in a mutant phenotype.
			C)	causes late-onset diseases.
			D)	a and b
			E)	a and c

(Questions 18-20)

Huntington disease (HD) is a lethal neurodegenerative disorder that exhibits autosomal dominant inheritance. Because the onset of symptoms is usually not until the third, fourth, or fifth decade of life, patients with HD usually have already had their children, and some of them inherit the disease. Now that the gene for HD has been identified and cloned, a direct genetic test can be performed to inform people in an HD family of their genetic status. The mutation that causes HD is an expansion of CAG repeats within the coding sequence of the gene. The normal allele contains up to 34 repeats, while disease-causing alleles carry 42 or more repeats. These repeats always expand, never contract. In a particular HD family, a young woman in her early 20s has a mother whose brother is exhibiting symptoms of HD. The mother is 38 years old, has not been tested for HD and is not currently exhibiting any symptoms. There is no history of HD on the father’s side of the family.

18			What is the probability that the young woman has inherited a disease-causing HD allele? Need a Hint?
			A)	1/16
			B)	1/8
			C)	1/4
			D)	1/2
			E)	1
19			The young woman decides to get tested for the mutant HD allele. DNA is isolated from a blood sample, the repeat region is amplified by PCR, run on a gel, and stained with ethidium bromide. The results are shown below:   size markers sample DNA       60 repeats __ __       50 repeats __         40 repeats __         30 repeats __ __ Will the young woman have HD? Need a Hint?
			A)	yes
			B)	no
			C)	no, but her mother will
			D)	can't tell
20			Will the young woman's mother have HD? Need a Hint?
			A)	yes
			B)	no
			C)	can't tell, she needs to be tested
21			You are a leading forensics expert and have been called to a murder scene. The victim has been stabbed multiple times and lies in a pool of blood. There are drops of blood splattered around her. You CAREFULLY collect samples from each drop of blood and from the pool of blood. You take the blood back to the lab and analyze it. From the pool of blood and from some of the larger drops, you are able to isolate the DNA and perform a minisatellite DNA fingerprint analysis. These results tell you that the pool of blood is composed of the victim's blood and that some of the larger spots contain blood from someone else. In the meantime, the police have arrested a suspect and they send a blood sample over to your lab to analyze. When DNA from the larger drops of blood and DNA from the suspect were compared, all five polymorphisms identified by the minisatellite probe were identical in both the test sample and subject DNA. Polymorphism #1 is present in the population at 1/100; polymorphism #2 is present at 1/2,000; polymorphism #3 is present at 1/150; polymorphism #4 is present at 1/50, and polymorphism #5 is present at 1/10. How many people in a population of 6.5 billion could have dripped blood with these polymorphisms at the scene of the crime? Need a Hint?
			A)	1 or fewer
			B)	10-100
			C)	100-1,000
			D)	1,000-1,000,000
			E)	over 1,000,000

(Questions 22-25)

You are using positional cloning to identify a gene involved in hereditary breast cancer. You have access to a large family with many members that have developed breast cancer at an early age.

22			You have narrowed down the gene to chromosome 17, but need to localize it to a particular region of the chromosome. You have identified a series of SNPs along the entire length of chromosome 17. You genotype all living adult female members of this family and the pattern of SNP alleles you observe is indicated in the table below. (Note: males can get breast cancer also, but for the purposes of this experiment, you focus only on the female members of the family). individual phenotype SNP-A SNP-B SNP-C SNP-D 1 breast cancer 1 1 2 2 2 normal 2 2 2 1 3 normal 1 2 1 2 4 breast cancer 2 1 2 2 5 breast cancer 1 1 1 2 6 normal 2 2 1 1 7 normal 2 2 1 1 8 normal 2 1 2 1 9 breast cancer 2 1 2 1 10 breast cancer 1 1 2 2 11 normal 2 2 1 2 12 normal 2 2 1 1 13 breast cancer 1 2 1 1 14 normal 1 2 1 2 15 breast cancer 1 1 2 2 16 normal 2 2 1 1 Which SNP is closest to the breast cancer gene? Need a Hint?
			A)	A
			B)	B
			C)	C
			D)	D
			E)	equidistant between B and C
23			After locating the region of chromosome 17 that contains the breast cancer gene, you identify eight small regions within that region that could contain an actual gene. To help identify true genes, you perform a computational genomic sequence comparison between mouse and human DNA in each region. (Actual genes are more likely to be conserved between species). The results are indicated below. The extent of sequence homology is indicated by the number of +'s. region homology to mouse sequence 1 ++ 2 + 3 ++++++ 4 +++++++ 5 + 6 + 7 ++ 8 +++++++ Which region(s) is/are most likely to contain actual genes? Need a Hint?
			A)	3
			B)	4
			C)	8
			D)	3, 4, and 8
			E)	1, 3, 4, 7, and 8
24			Gene expression patterns can further pinpoint candidate genes. To determine what tissues your candidate genes are expressed in, you perform a Northern blot analysis, the results of which are shown below. B, L, and K refer to mRNA samples derived from breast, liver, and kidney tissue, respectively. Probes A, B, C, and D are DNA sequences from 4 different candidate genes. probe A            probe B            probe C            probe D B L K            B L K            B L K            B L K                                                                                                                                                                                                                             __                                                                                                                                                                                                                                                                                                                                                                                                                                   __                                                                                         __                                                                                                                                                                                                                                                                                                                                                                                                                        __ __                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    Which probe is derived from a likely candidate breast cancer gene? Need a Hint?
			A)	A
			B)	B
			C)	C
			D)	D
			E)	none of the probes
25			As a final test, finding that the DNA sequence of a particular gene is consistently altered in affected individuals and not in unaffected ones is good evidence that your candidate gene is indeed the one responsible for the disease phenotype. Look at the exon two sequences below from your favorite candidate gene in several breast cancer family members. Sequences shown are coding strand sequences, with reading frame indicated by spacing. Sequence differences are indicated in bold. normal: GAT CAA CCT GAC CTT GAA GCC normal: GAT CAA CCT GAC CTT GAA GCC normal: GAT CAA CCA GAC CTT GAA GCC affected: GAT GAA CCT GAC CTT GAA GCC affected: GAT CAA CCT GAC CTT TAA GCC Is this a good candidate gene for hereditary breast cancer? Need a Hint?
			A)	yes
			B)	no
			C)	can't tell