Biochem Winter 2010 Exam I

Front 1

What is the difference between genotype and phenotype?

Back 1

genotype is the genetic makeup of an organism and is made up by the summation of all the DNA

Phenotype (also called trait) represents the observable physical characteristics of an organism for example: your weight, having sickle cell, etc., it is affected by genotype and the environment

Front 2

What is a transition mutation?

Back 2

it is a point mutation in which a purine is replaced by a purine or pyrimidine with a pyrimidine

Front 3

What is a transversion?

Back 3

A point mutation in which a purine is replaced by a pyrimidine or vice versa

Front 4

What is a nonsense mutation?

Back 4

a point mutation which leads to the creation of a stop codon

Front 5

What is a missense mutation?

Back 5

A point mutation which results in the change of a single amino acid

Front 6

What is a frameshift mutation?

Back 6

when an insertion of deletion happens that is not a multiple of 3 in the coding region of a gene it shifts the reading frame = can change AA sequence

Front 7

What is a lethal mutation?

Back 7

mutations that cause death in the organism., a lot of dominant diseases are lethal when homozygous ex. Tay Sach's b/c individuals do not live beyond childhood

Front 8

What is a loss of function mutation?

Back 8

results in a loss of activity of the gene product, not all are complete loss of function, can be partial as well, most recessive disease in this category...ex. hemophilia B and CF

Front 9

What is a conditional mutation?

Back 9

mutations that depend upon environmental conditions for symptoms to manifest,

Front 10

What is a gain of function mutation?

Back 10

mutation that an result in increased activity or novel function of the gene product, could also result from a protein being produced in a novel location and having an impact on surrounding cells

Front 11

What is a dominant negative mutation?

Back 11

it in some way blocks normal gene activity, it is produced when a mutated gene produces a mutated product that interferes with function of the normal gene product produced by the other allele, occurs in genes whose products must function as multimers

Front 12

What is haploinsufficiency?

Back 12

occurs when a loss of function mutation produces a phenotype in the homozygote and the heterozygote, 50% of normal gene activity is present but is not sufficient to maintain normal phenotype

Front 13

What is an epigenetic change?

Back 13

not a mutation, it is a change in phenotype without a change in genotype, cannot be inherited

Front 14

What is a polymorphism?

Back 14

it is a relatively common mutation, present in more than 1% of the population

Front 15

What is a SNP?

Back 15

it is a single nucleotide polymorphism in which a single base polymorphism occurs (most common)

Front 16

What is a STRP?

Back 16

also called microsatellites, they are short tandem repeat polymorphisms, they are a specific number of short sequences (usually 2-5 bp) that are repeated in tandem (one right after the other) scattered throughout the genome

Front 17

What is a VNTR?

Back 17

also called minisatellites, variable numbers of tandem repeats, tandem repeats of longer segments of DNA (14-500 BP)

Front 18

What are CNV's?

Back 18

copy number variants, larger segments of DNA repeated (>1000-2 million BP)

Front 19

What is the molecular fingerprint of an individual?

Back 19

VNTR's serve as a great tool for indentiying a specific person because the number of repeated units varies from person to person but is unique for that one individual,

Front 20

What is a RFLP?

Back 20

restriction fragment length polymorphism, allows us to look at the length of restriction fragments to determine genetic markers, paternity cases, etc.

Front 21

What is the principle of segregation (first law) as described my Mendel?

Back 21

it states that sexually reproducing organisms possess genes in pairs and only one of those genes is passes on to the offspring. it also states that genes remain intact and distinct in the next generation, they are not blended

Front 22

What is the principle of independent assortment (second law)?

Back 22

genes that are located at different loci are transmitted independently (this really only applies to genes that reside on different chromosomes or very far apart on the same chromosome)

Front 23

When would you use the multiplication rule?

Back 23

when you want to know the probability of two events occurring together (AND)

Front 24

When would you use the addition rule?

Back 24

when you want to know the chance of one thing vs. another happening (OR)

Front 25

What is the Hardy-Weinberg equation?

Back 25

(p+q)squared=p(squared)+2pq+q(squared)=1

p+q=1

Front 26

What are the 3 main conditions required for the H-W principle?

Back 26

1)random mating
2)large population
2)no mutations, migration, or natural selection

Front 27

What is the proband (proposita if female) in a pedigree?

Back 27

it is the first person to be identified with the disease in question

Front 28

What are the 4 main characteristics of autosomal dominant diseases?

Back 28

1)Two sexes exhibit the trait in approximately equal proportions and both sexes are
equally likely to transmit the trait to their offspring.
2.) There is no skipping of generations, in general. For example, if a child exhibits
polydactyly, then one of his parents must also have had the disease. This produces a vertical transmission pattern where the phenotype is seen in one generation after another.
3. Father-to-son transmission of the disease gene is observed. The presence of at least one father-to-son transmission excludes X-linked inheritance.
4. Affected individuals transmit the trait to approximately half of his or her offspring. Unaffected couples do not transmit the trait to their children.

Front 29

What is occurrence risk?

Back 29

the risk of producing an affected child when no children have yet been produced

Front 30

What is recurrence risk?

Back 30

the risk of producing another affected child when at least one child with the disease has already been produced

Front 31

What is the inheritance pattern in most genetic defects in metabolism?

Back 31

autosomal recessive

Front 32

What are the 4 main characteristics of an autosomal recessive disease?

Back 32

.1)Disease is usually seen in one or more siblings, but not in earlier generations.
There is usually no prior family history of the disease. Most affected individuals
are children of phenotypically normal parents.
2. Males and females are equally likely to be affected.
3. On average, 1/4 of the offspring of matings between two heterozygous carriers
will be affected.
4. Consanguinity is present more often in pedigrees involving autosomal recessive
diseases, especially rare autosomal diseases.

Front 33

How do new mutations affect patterns of inheritance?

Back 33

child can be born with a dominant disease when the parents did not have the disease, this indicates that the disease arose from a new genetic mutation in the child which means there is a high occurrence risk for the affected child's offspring but a low recurrence risk for the parents of the affected child since they do not possess the affected gene.
achondroplasia is about 90% new mutations
NF1 = 50% New mutations

Front 34

How does germline mosaicism affect patterns of inheritability?

Back 34

happens when the germline of an individual consists of more than one distinct pop. of cells, in the parent some of the germ cells were mutated but not enough of the somatic cells were affected to produce a phenotype,
-several cases of osteogenesis imperfecti
the recurrence risk is higher in these individuals than it was with achondroplasia from a new mutation

Front 35

How does delayed age of onset affect patterns of inheritability?

Back 35

symptoms usually not seen until 30 years of age or later, usually affected individuals have already produced children before they even know they have the disease,
examples: Huntington's and hemochromatosis

Front 36

How does reduced penetrance affect patterns of inheritability?

Back 36

it is the proportion of individuals carrying a certain genotype that also display the affected phenotype,
example: retinoblastoma (90% penetrance)

people with the disease genotype may not show signs of the disease but can still pass it on to their offspring

Front 37

How does variable expression affect patterns of inheritance?

Back 37

concerns the severity of the disease and is independent of penetrance, it refers to the EXTENT of expression of a particular phenotype,
example: NF1, it is 100% penetrant with variable expressivity

Front 38

How does pleiotropy/heterogeneity affect patterns of inheritance?

Back 38

pleiotropy=a single gene exerts its effects of multiple aspects of the body,examples: CF, marfan, von gierke
heterogeneity=more than one gene can be responsible for the gene but only one is deficient in each person
example: Osteogenesis imperfecti can be cause by a mutation in one of 2 different genes (both genes are needed to make the functional collagen protein

Front 39

What is genomic imprinting?

Back 39

refers to the differential activation of genes depending on the parent they are from, the transcriptionally inactive genes are said to be imprinted

Front 40

Describe the example of genomic imprinting that results from a deletion on the long arm of chromosome 15.

Back 40

if deletion is inherited from the father=prader willi syndrome (SNRPN)
if deltion is inherited from the mother-angelman syndrome (UBE3A)

Front 41

What is anticipation?

Back 41

When a disease exhibits an earlier and earlier onset or more severe expression with subsequent generations,

example:myotonic dystrophy, fragile X, huntington's

Front 42

Describe the example of myotonic dystrophy as it relates to anticipation.

Back 42

it is caused by a trinucleotide repeat (CTG)expansion of the DMPK gene, the disease is not produced by the presence of the CTG repeat but a critical threshold in the number of repeats, 5-50 repeats=no expression
50-100 repeats=mild expression
100-2000=full myotonic dystrophy, the number of repeats often increases with each generation explaining the earlier onset and more severe symptoms, thought to be caused by slippage of DNA polymerase

Front 43

What is consanguinity?

Back 43

mating between related individuals
increases the frequency of autosomal recessive diseases

Front 44

what is genetic load?

Back 44

the decrease in fitness of the average individual of the pop. relative to the fittest genotype due to the presence of deleterious genes in the gene pool

Front 45

What are the phases of the cell cycle?

Back 45

G1, S, G2, M

Front 46

What happens in the G0 phase of the cell cycle?

Back 46

it is the period when a cell is "resting", it is metabolizing nutrients but not dividing, stimulation by a mitogen will cause the cell to re-enter the cell cycle and begin cell division

Front 47

What happens in the G1 phase of the cell cycle?

Back 47

cell enters this stage after stimulation by a mitogen (growth factor), cell begins to replicate non-chromosomal components to pass to daughter cell and begins making proteins needed for DNA replication

Front 48

What happens in the S phase of cell cycle?

Back 48

cell begins to replicate its DNA, each of 46 chromosomes is duplicated by the cell, DNA still loosely arranged in this phase

Front 49

What happens in the G2 phase of the cell cycle?

Back 49

cell continues to grow in size so it can divide into 2 full size daughter cells during mitosis, proteins needed for mitosis made, cell also double checks for errors in replication and repairs them if needed
if everything ok, cell enters mitosis

Front 50

What are the 3 phases of interphase?

Back 50

G1, S, G2

Front 51

Describe the contents of a cell entering the M phase of the cell cycle.

Back 51

the cell has duplicate sets of all 46 chromosomes and twice the amount of all non-chromosomal machinery of a normal non-dividing cell

Front 52

What are the stages of mitosis?

Back 52

prophase, prometaphase, metaphase, anaphase, telophase, cytokinesis

Front 53

What is a kinetochore?

Back 53

a protein complex that connects each chromatid to the mitotic spindle

Front 54

Describe prophase.

Back 54

individual chromosomes have condensed to the point that they are visible, microtubules begin to rearrange,

Front 55

Describe prometaphase.

Back 55

is marked by the point in which the nuclear membrane begins to break down so microtubules can make contact with the chromosomes, they bind to kinetochore proteins already present at the centromere of each pair of sister chromatids

Front 56

Describe metaphase.

Back 56

when chromosomes (maximally condensed) are all lined up at the metaphase plate, they line up parallel to metaphase plate,

Front 57

Describe anaphase.

Back 57

shortest phase of mitosis, sister chromatids are pulled away from each other into opposite poles of the cell,

Front 58

Describe telophase.

Back 58

chromosomes begin to decondense and nuclear envelope reforms

Front 59

Describe cytokinesis.

Back 59

begins during anaphase, usually done by telophase, divides cytoplasm in two resulting in 2 daughter cells (belt like bundle of actin called contractile ring tightens up and splits the cell in two)

Front 60

During S phase, what is the ploidy number of the cell?

Back 60

4n

Front 61

What is the ploidy of cells with 23 duplicated chromosomes?

Back 61

haploid (b/c only 23 genetically distinct chromosomes)
note: cells still denoted 2n, but considered haploid

Front 62

What is synapsis?

Back 62

the close pairing of maternal and paternal duplicated chromosomes during prophase I = crossing over

Front 63

What is the Lyon hypothesis?

Back 63

suggests that one of the 2 X chromosomes in females is randomly inactivated in every somatic cell

Front 64

Is X inactivation permanent?

Back 64

YES!

Front 65

Which sex is a mosaic for the X chromosome? Which is hemizygous?

Back 65

females-mosaics
males-hemizygous

Front 66

What are barr bodies?

Back 66

found in females they are a dense staining chromatin mass in somatic cells (represents inactivated X chromosome)

Front 67

Describe why someone with extra chromosomes would still have a problem. (why can't they just inactivate extra X chromosomes?)

Back 67

b/c X inactivation is incomplete, about 15% of the genes escape inactivation and remain active in all copies,

Front 68

What are pseudoautosomal regions ??

Back 68

PAR1 and PAR2 are examples, they are genes also found on the pseudoautosomal regions of the Y chromosome and are inherited like normal autosomal disorders, NOT SEX LINKED b/c females can inherit an allele that was originally present on the Y chromosome of the father, etc.

Front 69

What are the 3 main characteristics of recessive sex linked inheritance?

Back 69

1. The trait is much more frequent in males than in females
2. There is NOT father-to-son transmission of the disease gene. The presence of
father-to-son transmission excludes X-linked inheritance.
3. The disease can skip generations by being passed to carrier females.

Front 70

What are the 5 main characteristics of X-linked dominant diseases?

Back 70

1. Affected males cannot transmit the disease to their sons, but they transmit the disease to 100% of their daughters.
2. Females are twice as likely to be affected as males. However, the expression is less severe in female heterozygotes than in affected males.
3. Typical mating would be between a normal male and a heterozygous female.
4. Vertical transmission pattern
5. There is NOT father-to-son transmission of the disease.

Front 71

What are sex influenced traits?

Back 71

they are autosomal traits that are expressed more frequently in one sex than the other,
example: male pattern baldness more common in males b/c of hormone DHT

Front 72

What is a sex-limited trait?

Back 72

only one sex is affected, usually due to anatomical differences such as sperm immotility
note: mother could still carry affected gene for this and pass it on to her offspring

Front 73

What is homoplasmy?

Back 73

when a cell, by chance, receives either all normal MtDNA or all mutated mtDNA

Front 74

What is heteroplasmy?

Back 74

when a cell, by chance, receives normal and a mutated copies of mtDNA

Front 75

Where is mtDNA inherited from?

Back 75

the mother therefore for diseases caused by mutations in mtDNA they can only be inherited from the mother

Front 76

What tissues are especially affected by mtDNA mutations?

Back 76

cells and tissues most dependent on a continuous supply of ATP,
example: muscle tissue and CNS

Front 77

What is cytogenetics?

Back 77

the study of chromosomes and chromosomal abnormalities

Front 78

What is the leading known cause of pregnancy loss?

Back 78

chromosomal abnormalities

Front 79

What is a karyotype?

Back 79

an ordered display of 23 pairs of human chromosomes in a typical somatic cell

Front 80

How are chromosomes first classified?

Back 80

according to size with the largest being designated chromosome 1 and so on

Front 81

After size, how are chromosomes then classified?

Back 81

according to position of the centromere

Front 82

What is the p arm of a chromosome?
Q arm?

Back 82

p arm is the short arm
q arm is the long arm

all in relation to position of the centromere

Front 83

Describe what metacentric, acrocentric, and submetacentric mean.

Back 83

meta=centromere occurs near middle of chromosome
acrocentric=centromere is near the telomere
submeta=when the centromere reside somewhere between the telomere and the middle

Front 84

What is polyploidy?

Back 84

the gain of one or more entire chromosome sets

Front 85

What is triploidy?

Back 85

cells that contain 3 copies (3n) of each chromosome (69 total)
usually occurs as a result of fertilization of an egg by 2 sperm cells, usually lost before birth

Front 86

What is monoploidy?

Back 86

the loss of a chromosome set, not seen in humans

Front 87

What is aneuploidy?

Back 87

the gain of one or loss of a single chromosome
two major types:trisomy and monosomy

Front 88

What is aneuploidy usually caused by?

Back 88

by nondisjunction (failure of the 2 members of the chromosome pair to disjoin or separate) during meiosis

Front 89

What happens to fetuses with autosomal monosomies?

Back 89

they are always lethal

Front 90

Which 3 chromosomes are associated with trisomies?

Back 90

13, 18, and 21
they are compatible with survival to term in at least some cases, probably relates to the # of genes of these 3 specific chromosomes

Front 91

What is a translocation?

Back 91

the interchange of genetic material between nonhomologous chromosomes

-most common chromosomal abberations seen

Front 92

What are the 2 types of translocation?

Back 92

1)reciprocal
2)robertsonian

Front 93

What is a reciprocal translocation?

Back 93

there are breaks on 2 different chromosomes and then those broken off pieces swap places

Front 94

What is a balanced translocation?

Back 94

it is when the size of the "swapped" pieced between chromosomes is the same size

Front 95

What is so bad about translocations?

Back 95

the offspring of individuals carrying the abnormality are likely to have an affected phenotype (person with the translocation originally is not likely to develop a phenotype since no genetic material is lost)

Front 96

What are the 4 possible outcomes in the offspring of someone with a reciprocal translocation?

Back 96

normal G and P, abnormal G but normal P, monosomic for a portion of one chromosome and trisomic for a portion of another, or vice versa for the 2 chromosomes in question

Front 97

What is Robertsonian translocation?

Back 97

only occurs in 2 acrocentric chromosomes, loss of 2 short arms of the chromosomes and fusion of the long arms

Front 98

What are the acrocentric chromosomes? (which #'s)

Back 98

13, 14, 15, 21, and 22

Front 99

How many chromosomes do people with a Robertsonian translocation have?

Back 99

they have 45 because they lost 2 normal ones and gained a robertsonian one

Front 100

Is the phenotype of people with a robertsonian translocation usually affected?

Back 100

no because the p arms of acrocentric chromosomes contain only redundant information anyways

Front 101

How many genotypes can be seen in the offspring of individuals with robertsonian translocations?

Back 101

6

Front 102

What is a terminal deletion?

Back 102

involve a single break in the chromosome, end of the chromosome is lost due to the break

Front 103

What is an interstitial deletion?

Back 103

involve 2 breaks and loss of the genetic material between the breaks, the two ends then fuse back together forming a shorter chromosome

Front 104

What is a ring chromosome?

Back 104

if the deletion involves the tips of the chromosome they can fuse together producing a ring chromosome in one somatic cell (all daughter cells will have monosomy for the chromosome b/c the ring is usually degraded in the parent cell)

Front 105

What is an inversion?

Back 105

it is caused by 2 breaks occurring with the intervening DNA subsequently reinserting, but in an inverted fashion

Front 106

What is a pericentric inversion?

Back 106

an inversion that involves the centromere

Front 107

What is a paracentric inversion?

Back 107

an inversion that does not involve the centromere

Front 108

What sorts of problems do inversions cause?

Back 108

they are balanced rearrangements so they rarely cause a phenotype in the person but they do cause inability of chromosomes to pair normally during meiosis I

Front 109

All states require newborn screening for what 3 diseases?

Back 109

PKU, galactosemia, hypothyroidism

Front 110

WHat is the inheritance pattern of PKU?

Back 110

autosomal recessive

Front 111

What is the cause of PKU?

Back 111

deficiency in phenylalanine hydroxylase which is required for conversion of phenylalanine to tyrosine, phenylalanine builds up in the blood and is converted to phenylpyruvic acid=toxic to cells

Front 112

What's an important thing to do before heterozygote screening?

Back 112

identify a population at risk b/c it's not feasible to test everyone in the US

Front 113

What are the 2 routine methods of prenatal diagnosis?

Back 113

visual (US), fetal tissue analysis (CVS, amniocentesis, IVF diagnosis )

Front 114

What is the triple screen test and what can the results tell you?

Back 114

MSAFP (maternal serum alpha fetalprotein), hCG, and estriol (3 enzymes)
-provides a statistical risk assessment, but not definitive
-performed at 15-20 wks gestation
-lots of false positives

Front 115

What 2 things does the triple screen test require?

Back 115

maternal age and fetal # (twins, etc.)

Front 116

What is quadruple screen?

Back 116

triple screen test + inhibin A (levels higher in fetuses with down syndrome)

Front 117

What 2 factors are commonly used to assess recurrence risk?

Back 117

degree of relationship, severity of the disease

Front 118

What equation can you use to estimate heritability of a disease?

Back 118

h=2(Cmz-Cdz)