Genetics (Integration) Rapid Fire Genetics

Question 1

Answer 1

raised blood CK level

Question 2

Answer 2

X-inactivation

Question 3

Answer 3

False

Question 4

Answer 4

Spontaneous

Question 5

Answer 5

Absent

Question 6

Answer 6

Genetic drift

Question 7

Answer 7

No. Switch to safer drug

Question 8

Answer 8

AR

Question 9

Answer 9

False

Question 10

Answer 10

DNA

Question 11

Answer 11

**Younger than
Familial clustering of tumours (both)

Question 12

Answer 12

Mother is a DMD carrier

Question 13

Answer 13

There are no non-genetic factors at play

Question 14

Answer 14

Have genetic factors

Question 15

Answer 15

False

Question 16

Answer 16

XLR

Question 17

Answer 17

False

Question 18

Answer 18

False

Question 19

Answer 19

Variable expression

Question 20

Answer 20

D. Logic question tbh.

Question 21

Answer 21

Inherited from the father

Question 22

Answer 22

False

Diagnosis, prognosis, management, recurrance etc etc

Question 23

Answer 23

Environmental

Question 24

Answer 24

Variable Expression

Question 25

Answer 25

***Drift or flow***

Question 26

Answer 26

***Nuclear.*** ***Keyword is MOST***

Question 27

Answer 27

***2, ma and pa***

Question 28

Answer 28

***False***

Question 29

Answer 29

***Phenotype or protein***

Question 30

Answer 30

***All***

Question 31

Answer 31

***Genetic flow*** ***Just rmb genetic flow = migration***

Question 32

Answer 32

***False*** ***Where got population level mutation so fast one...***

Question 33

Answer 33

***Gene-environment***

Question 34

Answer 34

***False***

Question 35

Answer 35

***False***

Question 36

Answer 36

***AD or mitochondrial***

Question 37

Answer 37

***Variable expression*** ***Ngl...the answer is always variable expression???***

Question 38

Answer 38

***Don't travel la lame***

Question 39

Answer 39

***Environmental***

Question 40

Answer 40

***Yes***

Question 41

Answer 41

***Yes***

Question 42

Answer 42

***Selection***

Question 43

Answer 43

***LDL***

Question 44

Answer 44

***25%***

Question 45

Answer 45

***Non-dysjunction***

Question 46

**(VVVVVV IMPT)** Name 5 AD disorders "Familiar Families Amuse Nerdy Officers" [...] Name 5 AR disorders "Beta Cats Pheel Severely Sick" [...] Name 4 XLR disorders "Redgreen Girls Destroy Hamsters" [...]

Answer 46

(VVVVVV IMPT) Name 5 AD disorders "Familiar Families Amuse Nerdy Officers" ***FH*** ***FAP*** ***Achondroplasia*** ***NF1*** ***OI*** Name 5 AR disorders "Beta Cats Pheel Severely Sick" ***Beta-thalessemia*** ***Cystic Fibrosis*** ***Phenylketonuria*** ***SCID*** ***Sickle cell anemia*** Name 4 XLR disorders "Redgreen Girls Destroy Hamsters" ***Red-Green colour blindness*** ***G6PD deficiency*** ***DMD*** ***Haemophilia A*** ## Footnote Just die die memorize cuz questions assume u know the inheritance pattern. These are important for clinicals as well. FH = Familial Hypercholesterolemia FAP = Familial Adenomatous Polyposis coli NF1 = NeuroFibromatosis type 1 OI = Osteogenesis Imperfecta SCID = Severe Combined ImmunoDeficiency DMD = Duchenne Muscular Dystrophy

Question 47

23 year old male with paternal grandfather with G6PD deficiency is suitable for genetic counselling. T/F? [...]

Answer 47

*False* ## Footnote G6PD deficiency is XLR. Grandfather would have given y to father. father also give y to this patient. So, not indicated for genetic counselling

Question 48

4 types of phenomenas that can result from a blocked pathway 1. [...] 2. [...] 3. [...] 4. [...]

Answer 48

4 types of phenomenas that can result from a blocked pathway 1. ***Accumulation of a substrate*** 2. ***Accumulation of another substrate as a result of shunting*** 3. ***Lack of product*** 4.*** Secondary metabolic phenomenon***

Question 49

A child inherits all his/her mitochondrial DNA from his/her mother. T/F?

Answer 49

***T***

Question 50

A substitution is the most common mutation that occurs in DNA. T/F?

Answer 50

A substitution is the most common mutation that occurs in DNA. T/F? ***T***

Question 51

All cells that descend from that cell will have the same inactive X and same active X. T/F?

Answer 51

All cells that descend from that cell will have the same inactive X and same active X. T/F? ***T***

Question 52

All genes on the X-chromosome are subjected to X-inactivation T/F?

Answer 52

All genes on the X-chromosome are subjected to X-inactivation T/F? ***F***

Question 53

All the mitochondrial DNA are identical T/F?

Answer 53

All the mitochondrial DNA are identical T/F? ***F*** **Homoplasmy: All the mitochondrial DNA are identical (eg. All normal or all mutant) Heteroplasmy: More than 1 type of mitochondrial DNA is present (e.g. mixture of normal variant and pathogenic variant)**

Question 54

Carrier frequency in SG for B thalassemia major is [...]%

Answer 54

Carrier frequency in SG for B thalassemia major is ***3%***

Question 55

Children with down syndrome have increased risk of [...] problems

Answer 55

Children with down syndrome have increased risk of ***thyroid*** problems

Question 56

Common signs of Inborn Errors of Metabolism

Answer 56

Common signs of Inborn Errors of Metabolism ***Hypoglycemia*** ***Acidosis*** ***Encephalopathy (Chronic/acute), Mental retardation, Regression*** ***Sudden death*** ***Movement disorder, Weakness*** ***Liver failure*** ***Heart failure*** ***Dysmorphic*** ***Failure to thrive*** ***Very sick even though this is just a minor illness*** **More of failures rather than malformations**

Question 57

Common teratogenic drugs and toxins

Answer 57

Common teratogenic drugs and toxins ***Alcohol - any exposure cause CNS and developmental issues*** ***Thalidomide - first trimester exposure limb deformities*** ***Anticonvulsants: Valproate and Carbamazepine - neural tube defects. Avoid if possible. otherwise folate supplementation prior to conception reduce the risks*** ***Cytotoxics: increased risk for fetal death, growth retardation and malformation*** ***Androgenic hormones: Virilization of the genitalia in a female fetus*** ***Lithium: Epstein’s anomaly of the heart*** ***Warfarin: increased risk of brain, skeletal and growth abnormalities*** ***Isotretinoin and etretinate - increased risk for brain, face, cardiac abnormalities*** **i** ***ACE Inhibitors - Oligohydramnios, anuria, renal failure, hypotension, lung issues, fetal growth issues, miscarriage or perinatal death***

Question 58

Compare the differences between Discrete/qualititative and Quantitative Complex disease

Answer 58

Compare the differences between Discrete/qualititative and Quantitative Complex disease

Question 59

Complex Diseases are aka multifactorial diseases. T/F

Answer 59

Complex Diseases are aka multifactorial diseases. T/F ***T*** **Types of disease Population affected Single gene disorders 2% Chromosomal disorders 0.7% newborns Mitochondrial diseases rare Multifactorial diseases >60%**

Question 60

Define dynamic mutations, what does it result in?

Answer 60

Define dynamic mutations, what does it result in? ***Mutations that are are unstable when passed from one generation to another generation*** ***Anticipation***

Question 61

Define Genomic Imprinting

Answer 61

Define Genomic Imprinting ***Defined as a phenomenon where the expression of a gene is dependent on the parent of origin***

Question 62

Define single gene disorder, list the different types.

Answer 62

Define single gene disorder, list the different types. A single gene disorder is one that is caused by a defect in 1 particular gene ***Autosomal Recessive (AR)*** ***Autosomal Dominant (AD)*** ***X-linked (XL)*** ***Y linked (YL)***

Question 63

Define teratogenesis

Answer 63

Define teratogenesis ***The process by which congenital malformations are produced in an embryo or fetus.***

Question 64

Describe a GTG/GTW karyotype

Answer 64

Describe a GTG/GTW karyotype ***Human chromosomes are described alpha-numerically 1-22 autosomes 23 sex chromosome can also be described by the position of the centromere*

Question 65

Describe the Factors that affect frequency of variants in a population

Answer 65

Describe the Factors that affect frequency of variants in a population ***Selection - positive or negative*** ***Mutation - chance*** ***Genetic drift - the population size is sharply reduced (bottleneck effect)/ group splits from main population, found a colony (founder effect).*** ***Gene flow - migration***

Question 66

Describe the structure and function of chromosomes

Answer 66

Describe the structure and function of chromosomes ***Chromosomes are made of light and dark bands, P (short) arm and q arm:*** ***Centromere*** ***Telomeres at ends*** ***Coding genes*** ***Non-coding regions*** **They are involved in cell divison**

Question 67

Distinguish between Disruptions, Deformations, Malformations

Answer 67

Distinguish between Disruptions, Deformations, Malformations ***Disruption: A defect: an interference with normal developmental process*** ***Deformation: A defect: non-disruptive mechanical forces on a normal tissue/structure*** ***Malformation: A defect: intrinsically abnormal tissue(s)***

Question 68

Dominant Negative Effect: where the [...] produces an [...] which [...] Example: [...]

Answer 68

Dominant Negative Effect: where the ***pathogenic variant in one allele*** produces an ***abnormal product which interferes with the function of the normal product produced by the other normal allele*** **Example**: ***Osteogenesis imperfecta***

Question 69

Dynamic mutation is associated with [...]

Answer 69

Dynamic mutation is associated with ***anticipation*** "In genetics, **anticipation** is a phenomenon whereby as a genetic disorder is passed on to the next generation, the symptoms of the **genetic disorder become apparent at an earlier age with each generation**. In most cases, an increase in the severity of symptoms is also noted."

Question 70

Explain the mechanisms of genomic imprinting

Answer 70

Explain the mechanisms of genomic imprinting Modification of a gene depending on its parent of origin ***Methylation of CpG residues near the promoter region*** of the ***SNRPN gene*** occurs during the ***formation of ovum*** but not sperm alters the structure of the chromatin>less open>prevents transcription of maternal allele

Question 71

Females have more variable phenotypes in X-linked recessive because of [...]

Answer 71

Females have more variable phenotypes in X-linked recessive because of ***X-inactivation (Lyonization)*** ***Homozygosity (rare)***

Question 72

General causes of malformations?

Answer 72

General causes of malformations? ***Single gene, chormosome, multifactorial, mitochondrial disorders*** ***teratogens*** Who knows!

Question 73

Genomic imprinting is set during [...] Once imprinted, the signal is [...] and maintained during subsequent [...] This parent of origin imprint is only erased and reset in cells that [...]

Answer 73

Genomic imprinting is set during ***gametogenesis*** Once imprinted, the signal is ***set for life*** and maintained during subsequent ***DNA replication*** This parent of origin imprint is only erased and reset in cells that ***undergo gametogenesis***

Question 74

Germline mosaicism is said to occur when a person has at least [...] An individual who has germline mosaicism may have [...] of the disorder Implications on the risk of having an affected child: [...], there is a risk that the gametes produced will contain the pathogenic variant

Answer 74

Germline mosaicism is said to occur when a person has at least ***two genetically different cell populations*** An individual who has germline mosaicism may have ***no or little evidence ***of the disorder Implications on the risk of having an affected child: ***If cells containing the pathogenic variant exist in the gonad, ***there is a risk that the gametes produced will contain the pathogenic variant

Question 75

Give examples of dynamic mutations that give rise to diseases

Answer 75

Question 76

How is Metabolic syndrome screening done?

Answer 76

How is Metabolic syndrome screening done? **Newborn should be on full feeds Test done at day 2-5 of life, or at discharge Use a special filter paper card**

Question 77

How is Mitochondrial Genome related disease transmitted?

Answer 77

How is Mitochondrial Genome related disease transmitted? ***Through the maternal line***

Question 78

How to treat Mitochondrial Disease?

Answer 78

How to treat Mitochondrial Disease? **Treat the symptoms** **Some treatment may be therapeutic: Patients with complex I and/or complex II deficiency may benefit from oral riboflavin Supplements with ubiquinone (coenzyme Q10, ubidecarenone) are usually well tolerated and some individuals report a subjective benefit while on treatment. **

Question 79

In a female cell, only one X chromosome is active at any time T/F?

Answer 79

In a female cell, only one X chromosome is active at any time T/F? ***T***

Question 80

In most dominant disorders, the homozygotes are [...] than the heterozygotes In a few disorders, the homozygotes and the heterozygotes are [...] affected e.g. Huntington Chorea Multiple Endocrine Neoplasia I (MEN I)

Answer 80

In most dominant disorders, the homozygotes are ***more affected*** than the heterozygotes In a few disorders, the homozygotes and the heterozygotes are ***similarly*** affected e.g. Huntington Chorea Multiple Endocrine Neoplasia I (MEN I)

Question 81

Individuals with down syndrome are prone to early onset dementia. T/F? [...]

Answer 81

Individuals with down syndrome are prone to early onset dementia. T/F? ***True***

Question 82

Mitochondrial diseases due to: nuclear DNA mutations will manifest in [...] mt DNA mutations will manifest in [...]

Answer 82

Mitochondrial diseases due to: nuclear DNA mutations will manifest in ***childhood*** mt DNA mutations will manifest in late ***childhood/adult life*** Nuclear DNA accounts for more mitochondria, so it makes sense to appear earlier than mt DNA mutations.

Question 83

Mitochondrial disorders may present at any age. T/F?

Answer 83

Mitochondrial disorders may present at any age. T/F? ***T***

Question 84

Most down syndrome children are conceived by mothers less than 35 years. T/F? [...]

Answer 84

Most down syndrome children are conceived by mothers less than 35 years. T/F? ***True!!*** ## Footnote >35 years old higher risk but more children are born by mothers <35 years old, so in terms of absolute numbers, this statement is true.

Question 85

Most foetuses with Down Syndrome spontaneously miscarry. T/F? [...]

Answer 85

Most foetuses with Down Syndrome spontaneously miscarry. T/F? *True* 80%

Question 86

Name examples of diseases related to imprinting?

Answer 86

Name examples of diseases related to imprinting? Prader-Willi Syndrome Angelman Syndrome ***Prader-Willi Syndrome*** Rare genetic disorder Clinical features Intellectual disability Short stature Small hands and small feet Initial inability to feed that later develops into an insatiable appetite, thus predisposing to morbid obesity and all its health consequences

Question 87

Of the proteins in the respiratory chain [...] proteins by the nuclear genome [...] proteins by the mitochondrial genome

Answer 87

Of the proteins in the respiratory chain ***74*** proteins by the nuclear genome ***13*** proteins by the mitochondrial genome

Question 88

One group of diseases that show dynamic mutations is the [...]

Answer 88

One group of diseases that show dynamic mutations is the ***trinucleotide repeat diseases*** ## Footnote The opposite is true for the following diagram

Question 89

Outline the possible clinical presentations of chromosomal disorders

Answer 89

Outline the possible clinical presentations of chromosomal disorders ***Infertility*** (can’t conceive) - 2-4% of infertile couples have a chromosomal abnormality ***Spontaneous miscarriage*** - 15% of pregnancies end in miscarriages. Half of these miscarriages are due to chromosomal abnormalities (most of which are due to spontaneous mutations) ***Still Birth*** - 5% of stillborn babies have a chromosomal abnormalities ***Abnormal baby at birth*** - Present early in life with growth and development problems ***Normal*** ## Footnote Note that should parents conceive a child w problems, important to screen parental chromosomes to predict their risk of having another child w chromosomal variant

Question 90

Patients with genetic conditions often wander through the healthcare system for a long time before getting a correct diagnosis (i.e. a diagnostic odyssey.) What is the average length of a **diagnostic odyssey** in a mature healthcare system? [...]

Answer 90

Patients with genetic conditions often wander through the healthcare system for a long time before getting a correct diagnosis (i.e. a diagnostic odyssey.) What is the average length of a diagnostic odyssey in a mature healthcare system? ***3-5 years*** Not trivial question. Came out in exam LOL.

Question 91

Rubella in the 3rd trimester will not result in much permanent organ damage. T/F? [...]

Answer 91

Rubella in the 3rd trimester will not result in much permanent organ damage. T/F? ***True*** ## Footnote Most susceptible period is 3rd-10th week after conceiving (5th-12th week after last period) because that is when organogenesis happens.

Question 92

The proteins that make up the mitochondrial respiratory chain are encoded by both the nuclear and mitochondrial genome T/F?

Answer 92

The proteins that make up the mitochondrial respiratory chain are encoded by both the nuclear and mitochondrial genome T/F? ***T***

Question 93

The proteins that make up the mitochondrial respiratory chain are encoded by both the nuclear and mitochondrial genome. T/F?

Answer 93

The proteins that make up the mitochondrial respiratory chain are encoded by both the nuclear and mitochondrial genome. T/F? ***T***

Question 94

The Y Chromosome contains [...] genes, which code for only [...] proteins deletion of the [...] arm of Y chromosome gives rise to [...]

Answer 94

The Y Chromosome contains ***78*** genes, which code for only **i** proteins deletion of the q arm of Y chromosome gives rise to ***infertility*** ## Footnote Since females are fine without having a Y chromosome, the Y chromosome must code for genes that are either specific to male function or are nonessential

Question 95

What are the four tested diseases that are X-linked recessive

Answer 95

What are the four tested diseases that are X-linked recessive ***Red-green colour blindness G6PD deficiency Duchenne muscular dystrophy Haemophilia A*

Question 96

What are the general principles of the pathogenesis of **IEMs**?

Answer 96

What are the general principles of the pathogenesis of IEMs? Their signs and symptoms are a result of one or more of the following mechanisms: - ***Accumulation of a normal substrate*** -*** Accumulation of a minor substrate as a result of shunting*** - ***Lack of a product*** - ***Secondary metabolic phenomenon - shunting interferes with a different pathway***

Question 97

What are the risk factors for having a child with chromosomal disorders?

Answer 97

What are the risk factors for having a child with chromosomal disorders? ***Parental chromosomal structure/number*** ***Maternal age*** (increases with maternal age) - down's syndrome ^ ***Paternal age*** (weak contributor) - chance of point mutations increased ***The structure of genome*** - some regions more prone to errors and translocations ***Other genes*** - missing DNA repair genes etc

Question 98

What are the types and origin of chormosomal abnormalities? Give an example of a disease from each

Answer 98

What are the types and origin of chormosomal abnormalities? Give an example of a disease from each ***Types of abnormalities*** ***Numerical*** – **gains are better than loss, can gain one or two e.g. down's/or a whole set or two whole sets (usually fatal)** ***Structural*** – **pathogenic or benign e.g. Deletion of the end of chromosome 4 (4p- syndrome)->developmental delay, risk of seizure** ***Origin of abnormalities*** ***Constitutional*** **(i.e. born with) Trisomy 21, Monosomy X** ***Acquired*** (i**.e. not born with) Chronic Myeloid Leukemia and a chromosome translocation ,t(9;22).**

Question 99

What is a complex disease?

Answer 99

What is a complex disease? ***Complex*** = **a condition that cannot be explained by the effect of a single gene** ***Disease***= **a disorder of structure or function**

Question 100

What is Population Genetics?

Answer 100

What is Population Genetics? Population genetics is a field of genetics that studies ***the genetic variations within and between population and how it changes/remains over time and place***

Question 101

When do you suspect mitochondrial respiratory chain diseases?

Answer 101

When do you suspect mitochondrial respiratory chain diseases? **When the blood lactate is high** **When it fits one of the classic descriptions** **When there is a disease that is progressive and involves multiple organ systems** **Myopathic features such asptosis, external ophthalmoplegia, proximal myopathy and exercise intolerance, cardiomyopathy**, **Neurological features such as fluctuating encephalopathy, seizures, dementia, migraine, stroke-like episodes, ataxia, spasticity, sensorineural deafness, optic atrophy, pigmentary retinopathy** **Diabetes mellitus** **Mid and late pregnancy loss** many individuals do not fit neatly into one particular syndrome

Question 102

Which of these 5 viruses is the most common identifiable cause of congenital infection? Varicella Mumps CMV Rubella HIV [...]

Answer 102

Which of these 5 viruses is the most common identifiable cause of congenital infection? **Varicella** **Mumps** **CMV** **Rubella** **HIV** ***CMV*** ## Footnote Keyword is COMMON. Varicella only if mother suay suay kena infected 5days-2weeks before delivery MMR in NCIS, most individuals vaccinated. HIV low prevalence rate in general.

Question 103

Why do many AD disorders show variability in the phenotype, both within the family and between families?

Answer 103

Why do many AD disorders show variability in the phenotype, both within the family and between families? ***Incomplete/reduced penetrance*** amongst 100 females who all have a pathogenic BRCA1 variant, only 60 females will develop breast cancer ***Sex-dependent penetrance*** Amongst 100 males who each has a pathogenic BRCA1 variant, almost none will develop breast cancer ***Age-related penetrance*** Persons with NF-1 are born without any feature of the disease but all will develop significant features by age 20 years old. ***Variable expression*** (most common reason) Individuals with NF-1 have different numbers of spots, lumps, freckling Possible mechanisms Genetic heterogeneity Gene-gene interactions Gene-environment interactions

Question 104

Woman who has a son with DMD is almost always a carrier. T/F? [...]

Answer 104

Woman who has a son with DMD is almost always a carrier. T/F? ***FALSE!!! *** . ## Footnote Spontaneous mutation in 33% of DMD cases.

Question 105

WRT to Characteristics of AR Disorders, Parents of the affected are [...] and are usually [...] Both sexes are equally [...] In some AR conditions, heterozygotes may have [...]

Answer 105

WRT to Characteristics of AR Disorders, Parents of the affected are ***asymptomatic carriers*** and are usually ***phenotypically normal*** Both sexes are equally ***affected*** In some AR conditions, heterozygotes may have ***some mild manifestations but these features are not the full manifestation of the condition***

Question 106

X Chromosome contains [...] genes

Answer 106

X Chromosome contains ~***500*** genes Most of these genes are found only on the X chromosome (i.e. not found on the Y chromosome) A small number of genes on the X chromosome have a related copy on the Y chromosome So females and males have 2 alleles each

Question 107

X inactivation happens all the time. T/F?

Answer 107

X inactivation happens all the time. T/F? ***F***. Inactivation begins soon after fertilization and ends by the first week of development

Question 108

X-Inactivation can be reversed. T/F?

Answer 108

X-Inactivation can be reversed. T/F? ***F***. The process is random but once inactivated, the inactivation is permanent