Human Genetics

Front 1

Chromosomes are compact coiled DNA strands?
T or F

Back 1

True

Front 2

Chromatin is..

Back 2

DNA, Histones and nonhistone Proteins

Front 3

A karyotype is..

Back 3

A 'picture' of all of the chromosomes present in an individual cell as seen during mitotic metaphase arranged based on size and classification.

Front 4

An idiogram is..

Back 4

The same thing as a karyotype but it is more so based on banding patterns.

Front 5

Define metacentric

Back 5

A chromosome that has its centromere in the middle of the two arms.

Front 6

Define acrocentric

Back 6

A chromosome that has its centromere close to its end and thus divides the chromosome into a long arm and a very short arm.

Front 7

Define submetacentric

Back 7

a chromosome that has a centromere that lies between the middle and the end, but closer to the middle. "Off center"

Front 8

What is G-banding..

Back 8

With Gimesa stain following digestion of chromosomes with trypsin. Where dark regions are heterochromatic, late-replicating and AT rich. Both chromosomes in a pair will have the same banding pattern.

Front 9

What is Q-banding..

Back 9

Uses a flourescent dye.. quinacrine, which produces a simular product as G-banding. Except that the light and dark regions are reversed.

Front 10

What does a labeled chromosome look like from 'top' to 'bottom'?

Back 10

short arm
p2
p1
centromere
q1
q2
long arm

Front 11

Chromosome abnormalities are highest in newborns, stillborns or spont. abortions?

Back 11

Spontaneous abortions (60%), still borns (6%) and least in newborns (0.6%)

Front 12

List the 4 types of chromosome abnormalities..

Back 12

1. Autosomal (number 1-22_
2. Sex (x and y)
3. Numerical (extra or missing chromosomes - common)
4. Structural (breakage- rare)

Front 13

What is normal human chromosome number and the two types of numerical abnormalities?

Back 13

Haploid (n) - 23
Diploid (2n) - 46

Aneuploid (extra, trisomy, or missing, monosomy, chromosome)
Polyploid, multiples of n (tiploid or tetraploid)

Front 14

Non-disjunction at meiosis I will yeild...

Back 14

Two trisomy cells
Two monosomy cells

Front 15

Non-disjunction at meiosis II will yeild...

Back 15

Two normal cells
One monosomy cell
One trisomy cell

Front 16

What is Down Syndrome

Back 16

Trisomy 21 (47 chromosomes in total)
Most common abnormality (1/600)
67% Due to error in meiosis I

Front 17

The relation between Maternal age and Nondisjunction

Back 17

-Increased chance of nondisjunction with increasing age.

Front 18

Theories of Maternal age vs nondisjunction

Back 18

-Maternal selection (decreased selection of abnormal chromosomes)
- Acrocentic associations (acrocentric chros cluster)
- Delayed fertilization (aged oocytes)
- Oocyte milieu (hormonesaffect spindle and ND)

Front 19

Paternal effect on Aneuploidy

Back 19

- Increased risk of trisomy
slight increase in risk for sex chromosomes.

Front 20

What is FISH

Back 20

Specific DNA probes attached to fluorescent dye. Can locate on chromosomes in metaphase or interphase
Detect sub microscopic deletions
Aneuploidy detection in gametes and embryos.

Front 21

Chances of Nondisjunction in certain chromosomes

Back 21

- Can happen for every chromosome (common mechanism)
- Increased frequency for
Chromosome 21 and
XY disomy in sperm

Front 22

Autosomal Trisomies are mostly..

Back 22

- >90% Maternal

Front 23

Sex chromosome abnormalities are mostly..

Back 23

Paternal

Front 24

what is the recurrence risk for parents who have had one trisomic child?

Back 24

1-2% increased risk. due to..
Undetected mocaicism in a parent or non-disjunction genes.

Front 25

What is uniparental disomy

Back 25

Both copies of chromosomes from one parent. Both parents had a nondisjunction leaving one gamete with no chromosomes and another with two copies.
(2/1000 cases of CF #7 chro)

Front 26

What is a mosaic

Back 26

Two or more different cell lines.
Occurs from a MITOTIC nondisjunction after fertilization. Monosomic cell is usually lost.

Front 27

What is a Triploid and how is it formed?

Back 27

3n = 69 chromosomes
accounts for 20% spontaneous abortions.
-70% paternal, mainly dispermy
- 30% maternal, meiosis II error.

Front 28

What is a tetraploid

Back 28

4n = 92 chromosomes
Spontaneous abortions
origin- duplication of 2n zygote

Front 29

Structural abnormalities occur from

Back 29

chromosomal breaks including deletions, duplication, translocation, inversion

Front 30

Cri Du Chat Syndrom is..

Back 30

Ex of a deletion
5p- missing tip of chromosome 5. Severity depends on the size of the chunk that is missing.

Front 31

A robertsonian translocation is..

Back 31

Where there is a nonreciprocal translocation between two acrocentric chromosomes. Starts from a break at the centromere and then the long arms of the two chromosomes fuse.
- Carriers are normal (all essential genes are present), progeny of carriers are at risk.

Front 32

What is reciprocal translocation

Back 32

- Breaks in any two chromosomes and interchange parts. Carriers are normal with 46 chromosomes.
- Increased reproductive risks

Front 33

Meiosis and repiprocal translocations

Back 33

-Alternate: Diagonally seperate, gametes are normal and a carrier
-Adjacent 1: Vertically split. Each gamete will have a partial trisomy and partial monosomy.
- Adjacent 2: Horizontial split. Products are one monosomy and one trisomy.

Front 34

What is an inversion?

Back 34

Two breaks in one chromosome heal in inverted order.
- Carriers are normal with reproductive risk (crossing over occurs in a loop = deleted genes)
- Pericentric spans the centromere, Paracentric is on one side of centromere

Front 35

Achondroplasia, what is it?

Back 35

Most common type of dwarfism
- Autosomal dominant gene, 50% caused by new mutation
- Cartilage defect- limbs and face

Front 36

Characteristics of Autosomal Dominant inheritance

Back 36

- Each affected individual has an affected parent
- Each child of an affected individual has a 50% change of being affected.
- Always assume individuals are heterozygous.
- Increased risk of new mutations with increased paternal age.

Front 37

Apert Syndrom

Back 37

-Autosomal Dominant
- Mostly from new mutations
- No survivors
- Mental retardation and fusion of cranial bones, digits

Front 38

Brachydactyly

Back 38

- Short digits, decreased height,

Front 39

What is Expressivity

Back 39

Variable severity or age of onset for a disease. Can show little effects, full effects or somewhere inbetween.

Front 40

Huntington Disease

Back 40

- Disordered and involuntary movements, mental deterioration, variable age of onset.
- Trinucleotide repeat CAG at 4p. Normal 9-29 repeats, huntingtons is 36+. More repeats early age of onset.

Front 41

What is penetrance?

Back 41

A gene is not expressed 100% of the time. It is all or none. If it shows ANY effect the gene is said to be penetrant. Expressed as a percentage.

Front 42

What is anticipation?

Back 42

When a disorder increases in severity through generations.
- Repeat size increases through generations. Correlates with age of onset and severity.

Front 43

What is Bayesian Theorem?

Back 43

Method of calculating risk.
- Prior: based on knowledge of persons ancestors
- Conditional: takes into account special situations. Eg. age, biochem tests, affected or unaffected individuals.
Joint: product of prior + conditional
Relative: Joint prob / Sum of Joint prob.

Front 44

Autosomal Recessive genes

Back 44

Genetic disorders that occur when an individual is homozygous for a recessive gene that is harmful. Every affected person must have carrier parents.

Front 45

What is consanguinity?

Back 45

- Mating with a genetic relative.
- More likely to carry the same AutoRecs gene.
- First cousins share 1/8th of their genes.

Front 46

Cystic Fibrosis

Back 46

- Pancreatic enzyme abnormalities.
- Death by 20
- Gene on 7q cloned but over 1,000 diff mutations

Front 47

PKU
Phenylketonuria

Back 47

- Deficiency of enzyme phenylalanine hydroxylase so build up of phenyl alanine
- MR and seizure
- Screening at birth
- Low phen in diet.

Two enzymes control breakdown so two diff mutations can cause disease

Front 48

Parents and children
OR Siblings share what percentag of their genes?

Back 48

50%

Front 49

Hutterites are an example of..

Back 49

Inbreeding, isolated communities so high frequency of genetic disorders.
- 2nd cousins share 1/32 of their genes.

Front 50

Founder effect

Back 50

A small population is established from a larger one. Usually with no gene flow, little genetic diversity, and increased sensitivity to genetic drift.

Front 51

Define heterogeneity

Back 51

More than one gene is controlling the disease

Aa bb and aa Bb parents (both diseasaed) can create a Aa Bb baby (not diseased)

Front 52

X-Linked Recessive characteristics

Back 52

- Usually occurs only in males (one x)
- It is passed from affected male through all his daughters to half their sons.
- Never father to son transmission

Front 53

X-Linked Dominant

Back 53

- Heterozygous mothers pass on to both sexes w/ freq. 0.5
- Hemizygous males trasmit to daughters
- Every affected child has an affected parent
- Freq. in females is twice that in males if trait is rare.

Front 54

X- Inactivation

Back 54

- All heterozygous females are mosaics cuz of inactivation
- affected female offspring of affected male probably due to x inactivation.

Front 55

Lyon Hypothesis

Back 55

In somatic cells of female mammals, only one X chromosome is active. Inactivation of one X occurs early in embroy. It is random and fixed.

Front 56

Why are extra or missing chromosomes very common?

Back 56

Because sex chomosomes do not contain life threatening genes so many individuals survive to birth.

Front 57

Examples of Sex chromosome aneuploidy

Back 57

Kleinfelter - 47XXY (male)
Turner - 45 x (female)
47 XYY (male)
Trisomy X - 47 XXX (Female)

Front 58

Origin of Kleinfelter

Back 58

47XXY
Meiotic error in female or male parent.
- More X chromosomes = greater degree of mental retardation

Front 59

Origin of 47 XYY

Back 59

Meiotic non disjunction in male parent. OR Mitotic nondisjunction in zygote.

Front 60

Origin of trisomy X

Back 60

Meiotic nondisjunction, mostly maternal.
- Progeny are nearly always normal.

Front 61

Origin of turner syndrom

Back 61

45X
The only type of monosomy that survives.
Nondisjunction in the father

Front 62

What is an isochromosome

Back 62

It is chromatids in a metaphase chromosome that divide along the WRONG plane.

Front 63

Ring chromosomes in Turner syndrom

Back 63

small ring chromosomes found in some, but not all, cells. Chromosome looses telomers and ends fuse to form a circle retaining a centromere.

Front 64

Sex determination in males and females

Back 64

It only takes one Y to be male
Posessing one X is sufficient to be a woman.

Front 65

Why do sex chromosome abnormalities usually have a mild phenotype

Back 65

Usually only affects sex differentiation and reproduction...
Because X-inactivation is a mechanism for dosage compensation

Front 66

What is a Barr body

Back 66

The inactive X chromosome/s present in nucleus of every cell

Front 67

All genes on an inactive X chromosome are silent.
True or False

Back 67

False. Although chromosome is not active, some genes are still expressed.

Front 68

What is a sex limited trait

Back 68

Expressed in only one sex but gene is not X-linked.

Front 69

What is a sex influenced trait

Back 69

expressed differently, in degree of frequency, in males and females. Gene is not X linked.

Front 70

Describe dosage compensation for X genes

Back 70

X inactivation corrects the amount of genes expressed in females (2 x's) and males (1 x).

Front 71

What is the differences between sexes

Back 71

1. Genetic sex (X or Y)
2. Gonads (Ovary or teste)
3. Duct system (internal)
4. Phenotype

Front 72

A mammalian embryo is ______

Back 72

bipotential
- Embroy without a gonad develops as female unless something intervenes.

Front 73

The Wolffian body progresses to a male system in the presence of _______

Back 73

Testosterone. It is a positive agent.

Front 74

The mullerian body progresses to a female system, except in the presence of

Back 74

MRF: Mullerian Regression Factor...
Therefore development of a male system.

Front 75

What hormones influence the male genetalia

Back 75

Testosterone and DHT

Front 76

What is the testes determining factor

Back 76

Gene SRY and TDF located on the Y chromosome. Therefore when Y chromosome present, these genes are translated and bipotential embryo goes to male.

Front 77

How DO XY females and XX males occure

Back 77

1. During recombination, a part of SRY is transfered from Y to X and XX males develop.
2. During recombination SRY is lost from Y chromosome and XY females develop.

Front 78

When does meiosis begin in FEMALES

Back 78

in embryo
1st meiotic prophase by 14wks
majority at prophase by 17wks
- Primary oocytes are arrested.
- 1st meiotic division resumes after puberty

First division at ovulation
Second division after fertilization

Front 79

45X females have more or less eggs?

Back 79

They have less eggs for ovulation than normal. Usually run out by puberty.

Front 80

Meiosis in males begins...

Back 80

Begins after puberty and continues until death.

Front 81

Dizygotic twins arise from..

Back 81

Two seperate ova are fertilized by two seperate sperm. May run in the womans side of the family (or be caused by fertility drugs). Placentas can be seperate or fused but each has their own amniotic fluid.

Front 82

Monozygotic twins arise from..

Back 82

One sperm and one egg, split embryo. There is no genetic basis for this.
Split before 4 days, each has own placenta Chorion and amnion
Split between 4 and 8 days they share chorion and amnion, seperate placentas.
Split after 8 days, share all three and are mirror images.

Front 83

Conjoined twins

Back 83

Are monozygotic twins where the embryo split after 12 days. The later the split the more risky the pregnancy.

Front 84

Dizygotic twins and maternal age...

Back 84

Dizygotic twins are more likely in mothers aged 30-40.. and lower in Older and Younger mothers.

Front 85

Consequences of enzyme deficency...

Back 85

A mutant enzyme means that the precursors will accumulate (may be toxic in excess) and downstream products will not be produced. Deficiency.

Front 86

Most frequent inherited metabolic diseases are...

Back 86

Cystic Fibrosis (1/2500)
PKU (1/12000)
and MCAD (1/20,000)

Front 87

Untreated PKU symptoms

Back 87

mousy odor, mental retardation, hypopigmentation, rash, autistic behavior, HIGH BLOOD phenylalanine levels.

Front 88

Simple treatment for PKU

Back 88

Target your food choices. Each foods low in protein, specially proteins containing high levels of phenylalanine.

Front 89

Cause of PKU

Back 89

- Mutation in enzyme in liver that converts phenylalanine to tyrosine. Tyrosine is precursor to melanine.
Phe is needed for conversions to dopamine and other epinephrines.
- Mutation in MTHFR also causes PKU and has implications elsewhere (related coronary disease)

Front 90

Complementation analysis allows..

Back 90

Distinction among patients having same biochemical presentation (phenotype) done by fusing cell lines from different affected patients. If not corrected than patients are in the same "complementation group".

Front 91

Characteristics of the disease to be eligble for neonatal screening

Back 91

Must be common, diagnosis is not evident upon examination, sever imparment or death,and have a beneficial intervention.

Front 92

Characteristics of test
Neonatal screening.

Back 92

A test must exist that is able to identify individuals, 100% effective, Few false positives.

Front 93

Characteristics of screening system..
Neonatal screening

Back 93

Prompt testing and follow up, educated health professionals, benefit which exceeds costs.

Front 94

Heel prick blood test offered for..

Back 94

PKU, congenital hypothyroidism, biotinidase deficenccy, .. etc.

Front 95

What is maternal PKU

Back 95

The child did not inherit the gene for PKU but the mother has PKU and therefore the child was exposed to high levels of Phe in utero.

Front 96

HOw do they do newborn screening..

Back 96

Tandem mass spectrometry.

Front 97

Frequency and hardy weinberyyy

Back 97

Use frequency occurance in population to determine q2.

p+q = 1
p2 + 2pq + q2 = 1