Molecular Biology And Genetics

Front 1

Differentiate between Mendelian and Chromosomal Disorders

Back 1

Mendelian = sing gene, one or several base pairs

chromosomal = many basepairs, many genes

Front 2

Phenylketonuria: PKU

Back 2

autosomal recessive disorder caused by a deficiency in phenylalanine hydroxylase. Phenylalanine cannot be metabolized to tyrosine and therefore it accumulates.

Therapy to restrict Phe in the diet alleviates symptoms.

this is an example of environmental influence on phenotype.

Front 3

Name a Disease where Phenotype is affected by environmental factors.

(there are many! feel free to edit this card to add them if mentioned in class)

Back 3

Phenylketonuria - PKU

Front 4

Proband

Back 4

Person you are seeing in the clinic (the subject of the pedigree)

Front 5

Treacher Collins Syndrome

Back 5

Malar hypoplasia (underdeveloped cheekbones) down slanting eyes, defect of the lower eye lid, malformation of the external ear, deftness and cleft palate.

An example of Variable Expressivity

Front 6

Neurofibromatosis I

Back 6

Multiple cafe-au-lait spots, neurofibromas, Lisch nodules of the iris, axillary and or inguinal freckling, bony abnormalities, scoliosis, CNS tumors, learning disabilities, macrocephaly.

An example of new mutations (50%)

An example of Variable Expressivity

An Example of 100% penetrance

Front 7

Define Variable Expressivity and give examples.

Back 7

Different individuals can express or manifest the same mutant alleles in different ways and with varying degrees of severity (independent of environment)

Parent can give rise to more or lesser affected children.

Examples
Treacher Collins Syndrome
Neurofibromatosis

Front 8

Allelic Heterogeneity

Back 8

Different mutations at the same locus can result in variable expression of the disease.

RET and LMNA genes

Front 9

Locus Heterogeneity

Back 9

Disease Phenotype can be caused by mutations at different Loci

TSC1 = less severe
TSC2 = more severe

Front 10

Postaxial Polydactyly

Back 10

An additional digit

An example of Incomplete Penetrance (65%)

Front 11

Obligate Heterozygote

Back 11

A person who has parents and children with an autosomal dominant condition but does not express the condition.

This is an example of incomplete penetrance. It is obvious he has the allele since both his parents and children are affected

Front 12

Give an Example of Incomplete Penetrance

Back 12

Postaxial Polydactyly
BRCA1 and BRCA2

Front 13

Pleiotropy

Back 13

multiple phenotype effects in different tissues and organs are produced ina single gene mutation

example: Marfans Syndrome

Front 14

Give and Example of Pleiotrophy

Back 14

Marfans Syndrome

Front 15

What is the risk of a person with a de novo mutation having an affected child?

Back 15

50% - There is no chance of a homozygous dominant child.

Front 16

give an example of de novo mutation

Back 16

Achondroplasia
Neurofibromatosis

Front 17

De novo mutation increases with maternal age, paternal age, or both?

Back 17

paternal age, Female eggs are all developed at puberty and suspended.

Male sperm are constantly generated.

Front 18

Germline Mosaicism

Back 18

When mutant allele is present in germ cells but not in somatic cells.

Front 19

A man and a woman have no family history of an autosomal dominant condition, but give rise to an affected son. The man is so disgusted with his mutant creating wife that he leaves her for a prostitute he met in east Saint Louis. When the prostitute has a baby who is also affected, who is the terrible person? why?

Back 19

None of the 3 people are terrible except the man for leaving his wife. You shouldn't judge a persons character by their genetic makeup. shame on you.

This is an example of Germline mosaicism. The man's gametes are affected but not his somatic cells.

Front 20

Anticipation

Back 20

tendency for certain diseases to show progressively earlier onset and increasing severity in successive generations.

an example is Myotonic dystrophy which is caused by trinucleotide repeats (CTG) which accumulate, especially in female gametogenesis.

More CTGs = earlier onset + more severity.

Front 21

give an example of Anticipation

Back 21

Myotonic Dystrophy

normal <34 mild 50-150

Also Fragile X

Front 22

Tay Sachs Disease

Back 22

Caused by absence of hoxosaminadase A with subsequent accumulation of GM2 gangliosidase in the CNS.

10x more frequent in ashkenazi Jews

Example of ethnic cluster (nice way to say consanquinity)

Front 23

Risk determination

Back 23

For autosomal recessive disorder with no family history

Carrier Frequency(mom) x CF(dad) x 1/4

Front 24

X - inactivation occurs at what cell stage in females?

Back 24

Less than 100 cells

Front 25

Skewed X - inactivation

Back 25

If one of the X chromosomes has a mutation in a gene that normally enhances the proliferation, maturation, or life span of certain cells, then the cells of that lineage will have a nonrandom pattern of X inactivation that is weighted against the mutation-bearing X chromosome

OR

When one X is preferentially expressed relative to another. (This definition includes the possibility that a malformed X would be chosen in the case of a robertsonian translocation.)

Front 26

The risk of a woman carrying an allele for a rare X linked disorder having an affected child is what? Explain.

Back 26

25%

there is a 50% chance that she passes on the affected allele. but since girls have two X chromosomes, only male progeny will be affected. There is a 50% chance that she will have a boy.

50% x 50% = 25% YAY!

Front 27

What is Gower's sign? Would this be more likely to be seen in males or females?

Back 27

Gower's sign is the need to use hands in order to stand up in and is indicative of duchenne muscular dystrophy.

DMD is an X linked recessive disorder and therefore is much mroe common in males than females.

Front 28

Will females carrying a recessive disorder know they are a carrier?

Back 28

sometimes. In cases of skewed x - inactivation you will see effects. Muscular dystrophy has a number of risk factors for carrier females. In many conditions however there will be no signs or symptoms.

Front 29

Hypophasphatemic Ricketts.
What leads to the "hypo phosphate"

Back 29

The condition involves and inability for the kidney to resorp phosphorus which weakens the bones tendons and joint capsules.

Front 30

Would you be more likely to see at 4 year old girl with Incontinentia pigmenti or a 4 year old boy with the condition? Explain.

Back 30

You would be more likely to see a girl with the condition since it is X-linked dominant and Male Lethal. Although many boys will be affected, they will not be born.

Front 31

You see a boy in your office with Incontinential Pigmenti. Is he human? how has he cheated death?

Back 31

Yes he is human. The boy could have 1 of 3 possible conditions.

1.) Klinefelters XXY
2.) somatic mosaicism (mutation in somatic cells not gametes)
3.) a mild mutation

Front 32

Fragile X syndrome

Back 32

most common cause of autism.
prominaent jaw and large balls.
Common in males.

An example of anticipation!

CGG repeats in FMR1 region. full mutation is >200 nromal is <44

Front 33

Male-limited Precocious puberty is X linked or Autosomal dominant?

Back 33

is is autosomal dominant (we see male to male transmission.)

The genes affected are only expressed in males. This is why it would appear X-linked.

Front 34

Hemochromatosis affects men more than women? is it X-linked?

Back 34

No. Women get it jsut as much as men, but they do not show the same level of symptoms.

The treatment for hemochromatosis is phlebotomy. Girls do this once a month.

(I'd take hemochromatosis any day.)

It is an exacmple of a sex-influenced trait.

Front 35

How can twins be used to quantify the genetic contribution to a condition?

Back 35

If monozygotic twins are more concordant than dizygotic twins, there are likely genetic factors at play.

Front 36

Twins are a great way to tell if gnetic factors playa role in a disease, but what about testing for environemntal factors?

Back 36

If adopted children have similar conditions it is likely environmental.

e.g. Poor political acuity is seen in all of Michelle Bachmann's 6000 adopted children.

Front 37

Familial Clustering

Back 37

increased risk with increased degree of relation.

Front 38

Sex bias

Back 38

Example: If the condition is more likely in males or females.

If a female gets a condition that is more likely in males... the chance of having additional chidren with that condition increases.

Front 39

Does severity correlate with recurrence in multifactorial diseases?

Back 39

Yes (but not all)

eg cleft lip risk increases by double if there is bilateral effects as opposed to unilateral effects.

Front 40

is recurrence risk of a MF disease more or less than a mendelian disorder?

Back 40

It is less but not insignificant. 2.5 - 5%

Front 41

should you use the work risk in from of patients when birth counseling?

Back 41

no! use "chance"`

Front 42

Recessive Disorders tend to code for enzymes or structural proteins?

Back 42

Enzymes since 50% function is typically sufficient.

Front 43

Chromasomal abnormalities occur with what frequency?

Back 43

1 in 150 live births.

Front 44

Metacentric

Back 44

when the centromere occurs near the midle of the chromosome q=p

Front 45

Submetacentric

Back 45

when the centromere occurs somehwere between the middle and the tip q>p

Front 46

Acrocentric

Back 46

when the centromere is in the telomere region.

Front 47

Q-banding

Back 47

Quinacrine mustard, a flourescent dye, produces alternating bands of bright and dull fluorescence along human chromosomes.

Not used frequently

Front 48

G-banding

Back 48

Pretreating chromosomes with salt solutions and proteolytic enzymes then staining with standard blood stains such as Giemsa.

Front 49

R-Banding

Back 49

Reverse banding of G-banding as a result of heat treatment.

Front 50

Explain 5q23.2 as a location for a mutation.

Back 50

Chromosome 5
q arm
region 2
band 3
subband 2

Front 51

explain 46XX,del(15)(q12)

Back 51

deletion on band 12 of chromosome 15 of a female.

Front 52

explain 46,X,r(X)

Back 52

Female with one normal x and one right X

Front 53

C banding

Back 53

only expresses heterochromatin regions of DNA. Requires hydroxide treatment.

Front 54

NOR - banding

Back 54

requires silver stain. Highlights the satellites and stalks of acrocentric chromosomes.

Front 55

Where is rDNA located

Back 55

repetitive DNA is located at the telomeres.

Front 56

FISH

Back 56

flourescence in situ hybridization

-consists of flourescently labeling specific gene sequences using probe.

Front 57

CGH

Back 57

basically 1000 FISH at the same time.

Front 58

Anaphase lagging

Back 58

One of two homologous chromosomes may lag behind during anaphase division.

Front 59

Placental chromosomal mosaicism

Back 59

1% to 5% of chorionic villi samples show chromosoml mosaicism.

Front 60

Somatic Recombination

Back 60

very rare event which can lead to homozygosity where others are heterozygous.

An explanation for the 2nd hit in retinoblastoma.

Front 61

What is three ways to obtain complete triploidy?

Back 61

1.) normal egg + 2 sperm
2.) diploid egg + 1 sperm
3.) normal egg + diploid sperm

Front 62

Cri du Chat Syndrome is caused by what?

Back 62

terminal deletion of p arm of chromosome 5.

When you have a single chromosome break, the chromosomes with the centromere is replicated, but the other segment will be lost.

Front 63

What is the most common example of interstitial deletion? How does it work?

Back 63

Prader Willi syndrom consists of two chromosomal breaks in 15q.

Each break produces sticky ends which can fit back together.

Front 64

Paracentric inversion.

Back 64

Both breaks occur on one side of the centromere. Does not result in a loss of genetic material so phenotype is typically normal.


Does result in reduced fertility due to issues with homologous recombination in meiosis. It produces acentric and dicentric chromosomes which are unviable. The remaining two alternatives (normal or inverted) are balanced and give a normal phenotype

Front 65

Pericentric Inversion.

Back 65

Breaks occur on opposite sides of the centromere.

Phenotypically normal until reproduction. The chromosomes will only have 1 centromere so each is viable for birth, however deletions occur which can lead to spontaneous abortions and severe brith defects.

Front 66

Translocation

Back 66

Chormosomal breaks occur in different chromosomes, and each terminal segment can move to the other chromosome.

Front 67

Do reciprocal translocations cause issues in the patient? What about their offspring?

Back 67

reciprocal translocations are balanced so typically no. However, homologous recombination during meiosis can present problems in the offspring.

Front 68

Robertsonian Translocation

Back 68

a break occurs in an acrocentric chromosome. This leads to one chromosome attaching to another. Phenotypically these people are normal, but their offspring can have duplications or deletions during homologous recombination.

downsyndrome occurs this way frequently. So genetic testing must always be done.

Front 69

What is the recurrence risk for Down Syndrome if it is.

Trisomy 21
Robertsonian from mother
Robertsonian from father

Back 69

1%
10-15% - mother carrier
0-2% - father carrier

Front 70

Uniparental Disomy

Back 70

phenomenon only seen in humans where a diploid cell has both chromosomes from a single parent. Consists of isodisomy (same chromosome replicated) and heterodisomy (two chromosomes from the same parent.)

Front 71

Isodisomy

Back 71

Uniparental disomy where both chromosomes are derived from the same parental chromosome.

Front 72

Heterodisomy

Back 72

uniparental disomy where two different chormosomes are given to the offspring from the same parent.

Front 73

Angelmen syndrome and Prader Willi both have versions which are linked to uniparental disomy. Both are also the same deletion. Explain.

Back 73

30% of prader willi is a maternal disomy with no paternal component

A small number of Angelment syndrome is caused by a lack of maternal contirbution due to a paternal disomy of chromosome 15

The symptoms are different due to imprinting effects. some genes are expressed maternally some are expressed paternally.

Front 74

Imprinting

Back 74

The effect of a gene is determined by whether it was inhertied maternally or paternally.

Ex Angelmen vs prader willi

Front 75

Gravida

Back 75

A statistic listing the number of previous pregnancies. (including abortions)

Front 76

Alpha Thalessemia X-linked Mental retardation

Back 76

distinctive craniofacial defects,
genital abnormalities
hypotonia
missing ribs possible

X-linked recessive

can be seen in female as a manifesting carrier.

Front 77

Manifesting Carrier.

Back 77

Having one allele of a recessive mutation while showing the phenotype.

Front 78

Dosage compensation

Back 78

Since males are hemizygous for X linked genes and females have 2 copies of X linked genes, one must be inactivated in the females. (X-inactivation)

Front 79

Inactivated X chromosomes are called what?

Back 79

Barr Bodies

Front 80

Are lines of Blaschko the same as dermatomes?

Back 80

No (but its the same idea)

they are of embryonic orgiin and reflex the migration pattern of primitive ectodermal cells.

Front 81

Incontinentia Pigmenti

Back 81

X linked dominant disorder, lethal and males and a prime example of X inactivation mosaicism in females. Female carriers show patterns of mispigmentation along lines of blashko

Front 82

In the case of a balanced reciprocal translocation between an X chromosome and an autosome, which chromosome would be X-inactivated?

Back 82

The normal chromosome would be X inactivated.

This makes sense since if the abnormal chromosome would be inactivated, you would lose an autosome.

Front 83

Skewed X Inactivation.

Back 83

Where one X chromosome is predominantly selected or rejected.

Example reciprocal translocation between an X chromosome and an autosome. The normal chromosome will be deleted to preserve the autosome.

Front 84

Psuedoautosomal region.

Back 84

Present on p arm of both X and Y chromosome. It escapes X inactivation in females.

Front 85

How does x inactivation occur? (mechanism)

Back 85

The X-inactivation center located on the proximal protion of the q arm. Leads to the methylation of histones and cytosine residues.

Front 86

Turner Syndrome is associated with what?

Back 86

Horseshoe Kidney as well as short stature

Front 87

What is Turner Syndrome.

Back 87

One less X

characterized byhorseshoe kidney, short stature, webbed neck, low posterior hairline, heart defects, wide nipples, lymphodema of hands and feet.

Front 88

Kleinfelters syndrome

Back 88

an extra XXY

gynecomastea, small testicles,

can develop diabetes mellitus

Front 89

What does Para refer to in terms of pregnancies.

Back 89

The pregnancy made it to 20 weeks. Does not refer to successful birth.

Front 90

Name some characteristics of down syndome.

Back 90

Single transverse palmar crease.
Hypotonia
microcephaly
eyes spaced apart.
upslanting eyes
protruding tongue
5th finger clinodactyly
Absent moro reflex, no cry

Front 91

Why should you not freeze blood in a downsyndrome patient?

Back 91

You need to see the sell during mitosis whihc means you need to culture the cell. Frozen cells are dead cells.

Front 92

How do you stop anaphase in chromosome testing. You add cochicine to break the mitotic spindles?

Back 92

You add cochicine to break the mitotic spindles.

Front 93

How many basepairs are wrapped around each histone?

Back 93

147bp over two turns.

Front 94

What are some indicating features of Trisomy 18

Back 94

Rocker bottom foot
Small mouth
Tiny baby
low set ears.
Heart Murmur

Front 95

Can you freeze the sample for FISH?

Back 95

Yes you are suing interphase cells.

Front 96

Name three ways to get Turners Syndrome?

Back 96

45, X

X, rX (one X is a ring)

Mosaicism.

Front 97

What is the key difference of meiosis form mitosis (first thing)

Back 97

Homologous pairing (allows recombination)

Front 98

Nondisjunction in Meiosis leads to two chromatids in the germ cell... Are they of maternal or paternal orgigin or both when this occurs in Meiosis I? Meiosis II?

Back 98

Meiosis 1 = both

Meiosis 2 = paternal OR maternal

Front 99

Would you rather carry a paracentric inversion or a pericentric inversion? Why? The catholic church may sway your decision.

Back 99

I would prefer a paracentric inversion. Of my possible gametes, 2 will always be spontaneous abortions, one will be totally normal, and one will be likely phenotypically normal, but carry the inversion.

In a pericentric inversion, the likely hood of producing offspring is higher, but there is a chance that the child will have severe developmental deformities.

Front 100

In the case of down syndroms what genetic test should you prefer?

Back 100

Chromosome. It will differentiate between trisomy 21 or a robertsonian translocation of 21 to 14.

Front 101

when is a 45 female phenotypically normal?

Back 101

If she carries a robertsonian translocation. Eg 21/14 which would lead to downsyndrome in kids.

Front 102

What is the risk of a mother carrier having an affected child?

Back 102

15% empirically

logically it is 30%

Front 103

Can a woman with turner Syndrome have a child?

Back 103

Yes if the egg is donated.

Front 104

How is intelligence affected in Turners syndome.

Back 104

really not bad... some difficulty with math. and apacial relationships.

Front 105

What is the genetic inheritance of Fragile X?

Back 105

It is more frequent in males as a result of CGG repeats.

Front 106

what should you warn female carriers of fragile X about?

Back 106

early menopause.

Front 107

What will a southern blot show in fragile x syndrome.

Back 107

Massive blot.

Front 108

What will PCR show in fragile x syndrome?

Back 108

No band because its restrction sites are too far apart.

Front 109

Fragile X-associated tremor/ataxia is what type of mutation?

Back 109

A pre-mutation (Fragile X requires 200 repeats.) what if there are 150 repeats?

Front 110

Huntingtons, myotonic dystrophy, and fragile X express what?

Back 110

Anticipation - increasing amount of terminal repeats.

Front 111

hairy ears is not X linked... what isit?

Back 111

Y linked.

Front 112

Population genetics

Back 112

study of distribution of genes and the factors that maintain or change the frequency of genes.

Front 113

Homogeneity in population genetics leads to what?

Back 113

Extinction

Front 114

Ethnic group

Back 114

human groups which developed characteristic sets of gene frequencies resulting from geographic and genetic isolation.

A tool for calculating risk

Front 115

Genetic epidemiology

Back 115

Seeks to elucidate the role of genetic factors and their interactions with environmental factors in the occurance of disease in population

Front 116

what is the genetic difference from human to human? Human to chimpanzee?

Back 116

.1% human to human. 1% human to chimpanzee

Front 117

Alu elements

Back 117

short stretch of DNA which repeated. key to evolution. linked to cancer and diabetes.

Front 118

Tay sachs is found in what population?

Back 118

Ashkanazi jews are 100x more common.

Front 119

ADH2 is found in the what population what does it do?

Back 119

Japan- alcohol intolerace.

Front 120

deltaCCR5

Back 120

cell surface cytokine receptor. Confers resistance to HIV infection in homozygotes.

Front 121

Allele frequencies

Back 121

Calculated based on number of alleles not jsust number of people.

Allele frequencies always add to 1

Front 122

Genotype frequency vs allele frequency

Back 122

Genotype is people with a genotype... allele is alleles

Front 123

Will dominant alleles have a higher or lower frequency that the recessive?

Back 123

Not always. Think about huntingtons... dominant will kill you!

Front 124

What are the five conditions fo hardy-weinburg equilibrium?

Back 124

1.) Large Population
2.) Random Mating
3.) No change in allelic frequency due to mutation
4.) No immigration or migration
5.) No natural Selection

Front 125

What is the law of addition?

Back 125

Combined probabilities which are mutually explusive.

key word OR

Front 126

What is the law of multiplication?

Back 126

two or more events are dependent.

Key word AND

Front 127

how do the 3 genotypes fit into hardy weinberg?

Back 127

AA = p^2
Aa = 2pq
aa = q^2

Front 128

Stratification (as an exception to random mating)

Back 128

e.g races or religions

Front 129

Assortive Mating

Back 129

Choosing a mate because he/she posesses a specific characteristic

Front 130

What are 3 exceptions to random mating?

Back 130

Stratification
Assortative Mating
Consanguinity

Front 131

Fitness

Back 131

number of offspring of affected individuals who survive to reproductive age. (from 0 to 1)

Front 132

Selection

Back 132

1-fitness

It measures the loss of fitness of having an allele.

If f=0 selection is completely against proppagation of the allele

Front 133

When s = 1 what is happening.

Back 133

The allele completely kills the person's reproductive capability. fitness is 0

Front 134

What are 4 exceptions to constant allele frequency?

Back 134

1.) Mutation
2.) Selection
3.) Genetic Drift
4.) Gene Flow/Migration

Front 135

What are the clinical consegquences of the delta hemoglobin chain mutation?

Back 135

There are none. Delta chains are rarely found in the blood.

Front 136

Which globin gene families diverged first?

Back 136

alpha and beta globin genes.

Front 137

how many alpha globin genes does a normal person have?

How many beta globin genes does a normal person have?

Which globin product predominates?

Back 137

There are 4 alpha genes and 2 beta genes. Alpha genes slightly predominate but they are almost equal.

Front 138

What does Hb Mckees Rocks tell us?

Back 138

Hb McKees Rocks is the result of a premature stopcodon affecting the C terminal domain. It results in decreased subunit cooperativity suggesting that the C terminal is important for cooperative binding.

Front 139

What causes sickle cell anemia?

Back 139

a point mutation in the beta globin gene which replaces glutamate with valine at position 6.

Charged to uncharged can lead to folding issues.

Front 140

What would happen to Hb F if it were affected with sickel cell anemia?

Back 140

It is not affected, infact it is strongly resistant and used as a therapy for Sickle Cell Anemia

Front 141

What major symptoms are associated with sickle cell? Why?

Back 141

All diseases which could result from capillary occlusions are seen in sickle cell.

These include:
Stroke
Renal Failure
Splenic Faire
Bone Infarctions
Pneumonia
and others.

The anemia occurs because sickle cells are removed from circulation mroe efficiently than normal red blood cells.

The chronic hemolysis can lead to gall stones. due to increased billirubin levels.

Front 142

Where is sickle cell most common?

Back 142

Subsaharan Africa, India, Arabian peninsula.

Very similar to areas in which malaria is endemic.

Front 143

how does Hb C differ from Hb S

Back 143

Hb C does not form beta chain dimers leading to sickling. It does however form unstable hemoglobin that forms crystals which target it for hemolysis.

Hb C is stypically mild compared with sickle cell, but problems with the spleen and gall stones still occur.

Front 144

Hb New York and Hb Boston are characterized by what?

Back 144

Decreased oxygen affinity. Who can breath in those polluted cities anyway?

Front 145

Hb York, Hb Hiroshima, and Hb Chesapeake, and Hb F are characterized by what?

Back 145

Increased oxygen affinity. Aside from hiroshima, these are all fresh air places in my mind.

Results in not enough offloading to the tissues.

Front 146

What happens in methemoglobinemia?

Back 146

Heme iron switching from the ferrous state (+2) to the ferric state (+3) This means it cannot bind Oxygen properly

Front 147

What is the bodies defense to methemoglobin

Back 147

NADH methemoglobin reductase (Diaphorase I)

Front 148

How does alpha thallasemia in the african population differ from alpha thallesemia in the Asian population.

Back 148

The asian population can have mutation in both genes (all 4 copies) Whereas the African population only has mutation of 1 gene on chromosome 16.

Front 149

What is the clinical manifestation of alpha thallesemia.

Back 149

The production of beta globin tetramers in adults (Hb H) and gamma globin tetramers (Hb Barts) during fetal life.

Front 150

Hb H

Back 150

beta globin tetramers. a common response to alpha thallesemia in adults

Front 151

Hb barts

Back 151

gamma globin tetramers. A common response to alpha thallesemia in fetal life

Front 152

Hb M

Back 152

congenitally derived methemoglobin which has iron held in its ferric (3+) state and is unable to bind oxygen well.

Front 153

Explain the increasing severity of alpha thallesemia.

Back 153

1 mutation - typically silent
2 mutations - mild microcytic anemia some Hb Barts
3 mutations = chronic hemolytic anemia - high Hb Barts, noticible Hb H
4 mutations Hydrops fetalis. death. all Hb Barts - no adult life.

Front 154

hydrops fetalis

Back 154

Excessive fluid buildup resulting from severe alpha thallesemia in asia.

Front 155

Is beta thallesemia fatal?

Back 155

typically no. though left untreated it will result in a shorter lifespan.

Front 156

What are symptoms of beta thallesemia?

Back 156

Splenomegally and increased bone marrow space. Growth is impeded, severe iron overload.

Front 157

Beta tetramers are an issue in alpha thallesemia, how about alpha tetramers in beta thallesemia?

Back 157

alpha tetramers are very unstable and are removed almost immediately. you will not see these tetramers.

Front 158

Where is beta thallesemia found?

Back 158

southern europe and north africa (think mediteranean sea "thalassa = sea"

Front 159

Hb E

Back 159

results from a point mutation of glutamate for lysine at position 26 (opposite charge) of the beta globin gene. The E chain is fully functional, though the mutation leads to premature stop codons.

Heterozygotes have 75% hemoglobin production with 1/3 of the Hb being of HbE type

Homozygotes have 50% hemoglobin function with all Hb E. Symptoms are similar to beta thllesemia minor.

Common in Thailand

Can mix with beta thallesemia. to form mixed heterozygotes. HbE/B0 = 25% production of pure HbE

Front 160

If a child inherits an allele for beta thalesemai and a gene for HbE what will happen?

Back 160

The child will have 25% normal Hb production with all of the Hb being Hb E.

This is equivalent to thalassemia intermedia with noticable anemia.

Front 161

what is the difference between B0 thalassemia and B+ thallesemia.

Back 161

B+ is amutation int he promoter and can still result in some beta globin production.

B0 is amutation in the beta globin gene and results in no beta globin.

Front 162

beta thallesemia combined with alpha thallesemia causes what?

Back 162

A sometimes milder effect since the major issue with thallesemia is whether alpha globin is produced at a ratio higher than 2:1

Front 163

How much does sicke cell trait prevent malaria infection.

Back 163

not at all. Sickle cell trait makes the efffects of malaria less lethal.

Front 164

when will beta thalasemia symptoms being to appear?

Back 164

6 months of age

Front 165

On the pedigree what is a tell tale sign of mitochondrial inheritance.

Back 165

Only Mothers pass on the disease. No paternal inheritance.

Front 166

homoplasmy

Back 166

All the mtDNA in a cell or tissue is similar

Front 167

Heteroplasmy

Back 167

More than one type of mtDNA within a cell.

Front 168

What organs/cells will be most affected by a mtDNA mutation?

Back 168

cells which require the most ATP
-CNS
-Striated and cardiac muscle
-Kidney
-Liver

Front 169

Mosaicism in turner syndrome sometimes requires profylactic removal of gonads. When is this the case?

Back 169

If there is mosaicism for XY. The streak gonads can lead to neoplasms.

Front 170

what is the most common chromosome involved in uniparental disomy?

Back 170

Chromosome 15

Front 171

Angelmen syndrome and Prader willi syndrome are examples of uniparental disomy of the same chromosome... Explain how they are different.

Back 171

Angelmen is from the Maternal chromosome 15

Prader Willi is from the paternal chromosome 15

Front 172

What is Trisomy rescue.

Back 172

When there is a trisomic event usually from the mother which is followed by anaphase lag which returns the cell to diploid state.

UPD can result.

Front 173

Epigenetic

Back 173

referring to things not coded in the gene sequence such as methylation. (IMPRINTING is epigenetic)

Front 174

Genomic Imprinting

Back 174

phenomenon that causes functional differences between paternal and maternal gametes. Often methylation of histones and cytosine bases.

the imprinted allele is NOT expressed.

Front 175

Complete hydtidiform mole

Back 175

when an egg which lacks a nucleus is fertilized by a 23 X sperm.

Front 176

Ovarian Teratoma

Back 176

contains only maternal chromosomes which duplicate and divide.

Front 177

Is imprinting passed on form generation to generation?

Back 177

No, it is erased in primordial germ cells.

It will be reset based on how the allele is passed on.

Front 178

Beckwith-wiedeman syndrome

Back 178

excess of paternal or a loss of maternal contribution of genes on chromosome 11p15.

Encodes IGF2 which is implicated in tumor growth.

Front 179

Explain the inheritance pattern of imprinted alleles?

Back 179

Paternally imprinted allele mutations will not be seen in children who receive the paternal allele.

You expect roughly euql number of affected males and females from generation to generation.

Can appear to be autosomeal dominant with incomplete penetrance.

Front 180

List 5 examples of nonmendelian inhertiance.

Back 180

Mitochondrial
Imprinting
trinucleotide repeats
Mosaicism
Uniparental disomy

Front 181

Can mitochondria full function without nuclear DNA?

Back 181

No!

Front 182

How many genes are in the mt genome?

Back 182

37

Front 183

Considering heteroplasmy, how does a mt mutation lead to a phenotype?

Back 183

There are threshold levels that need to be acheived before effects are seen.

Front 184

If mitochondria replicate and segregte at random how can a mutation manifest when there are many mitochondria per cell.

Back 184

The mutation may enhance replication rate. In successive generations if can take over.

Front 185

Port wine stain are seen in what?

Back 185

Sturge-Weber Syndrome an example of mosaicism.

looks like god spilled wine when making the affected patient.

Front 186

Isodisomy as a result of meiotic nondisjunction would occur in meiosis I or meiosis II?

Back 186

Meiosis II

Front 187

Heterodisomy as a result of meiotic nondisjunction would occur in meiosis I or meiosis II?

Back 187

Meiosis I

Front 188

what are the 5 goals of genetic counseling?

Back 188

1.) Facts: Diagnosis, Course, Therapies
2.) Inheritance - risk of recurrence
3.) Options for risk of recurrence
4.) relationship effects, beleifs etc
5.) best adjustment therapy for affected child

Front 189

What are four time settings for Genetic counseling?

Back 189

Preconception
Prenatal
Pediatric
Adult

Front 190

Simply what is the 4 step process of gnetic counseling assuming all are appropriate.

Back 190

1.) Diagnosis - always
2.) Occurrence/Recurrence Risk Assessment
3.) Communication
4.) Follow-Up

Front 191

Genetic history is more extensive than a typical medicla history what are 5 features that are important?

Back 191

1.) Pregnancy history
2.) Past Medical History
3.) Diet History (Fetal alcohol synd)
4.) Developmental History
5.) Family History

Front 192

What advice should you give your patient/family during genetic counseling.

Back 192

As a professional, Do not give advice! Give information.

Front 193

child with down syndrome or down syndrome child or simian?

Back 193

Child with down syndrome

-it emphasises humanity

Front 194

Risk or Chance?

Back 194

chance

risk invokes thoughts of danger

Front 195

95% chance of normal or 5% chance of affected?

Back 195

95% chance of normal

5% is a very scary number and many times it shoudnt be.

Front 196

What is chorionic villi sampling

Back 196

Transcervical or transabdominal ultrasound guided cannula or needle aspiration of chorionic villi. Performed at 10-12 weeks. Allows indirect assesment of fetal chromosomes and single genes.

Front 197

What is an amniocentesis

Back 197

Transabdominal needle aspiration of amniotic fluid with ultrasound guidance. Performed at 15-20 weeks

Front 198

What is Bayesian Analysis?

Back 198

Take family into consideration. Likely hood of inheritance to occur based on family history.

Front 199

Is screen positive a diagnosis?

Back 199

No it is a red flag.

AFP can screen positive like crazy for down syndrome. (I was screen positive, I only mostly have downs.)

Front 200

Soft Signs can be a good or bad thing? how could they be bad?

Back 200

some signs can be completely normal but are alos linked with major illnesses. They can lead to undue stress.

Front 201

which is done first, CVS or Amnio?

Back 201

CVS - 10-12 weeks
Amnio closer to 16 weeks.

Front 202

A man is affected with an X-linked dominant disorder. The disease has a penetrance of 60% by the
time one reaches reproductive age. Assuming that he has children with an unaffected woman (does
not have the altered gene), what is the probability that any of his daughters will be affected with this
disorder by the time they are ready to consider having a family of their own?

Back 202

60%


100% of his daughters will receive the altered gene and 60% will
eventually have phenotypic expression of the disorder.