Unit 2 Pathophysiology - Chapter 4 Genes and Genetic Diseases

Question 1

DNA - four nitogenous bases

DNA, RNA, and Proteins: Heredity at the Molecular Level

Answer 1

adenine, cytosine, guanine, thymine [uracil - RNA]

Question 2

DNA polymerase

DNA, RNA, and Proteins: Heredity at the Molecular Level

Answer 2

replication; adds bases to new strand, performs proofreading fx

Question 3

Mutation

DNA, RNA, and Proteins: Heredity at the Molecular Level

Answer 3

inherited alteration of genetic material

Question 4

Mutagens

DNA, RNA, and Proteins: Heredity at the Molecular Level

Answer 4

substances that causes mutations; radiation, chemicals (nitrogen mustard, vinyl chloride, alkylating agents, formaldehyde, sodium nitrate)

nitrogen mustard strongest while sodium nitrate weakess

Question 5

Phenylketonuria

DNA, RNA, and Proteins: Heredity at the Molecular Level

Answer 5

infant born w/ inability to metabolize amino acid phenylalanine (single gene d/o) and this amino acid can accmulate in the infant’s brain causing irreversible intellectual disability

limit foods such meat, fish, eggs, milk, cheese, nuts and pulse

The first line of treatment may include a low-protein diet. Infants may need special formula to control the amount of protein they eat. As your child grows older, he or she may need to use a formula supplement to ensure that they are getting enough protein.

Question 6

Transcription

process by which DNA specifies a sequence of mRNA.

Answer 6

transcription is to make a RNA copy of a gene’s DNA sequence.

Question 7

Introns vs exons

process by which DNA specifies a sequence of mRNA.

Answer 7

Excised seqeunces vs remaining strand for coding of proteins

Question 8

MicroRNAs (miRNAs)

Answer 8

7 to 27 nucleotides in length, that bind to specific mRNA sequences and down-regulate their expression.

Question 9

long noncoding RNA (lncRNA)

process by which DNA specifies a sequence of mRNA.

Answer 9

greater than 200 nucleotides; a non translated RNA => genome contains 10,000 lncRNA and can be involved in gene regulation

Question 10

Translation

process by which DNA specifies a sequence of mRNA.

Answer 10

RNA directs synthesis of polypeptides (takes place in ribosome)

Question 11

Body cells? Sperm + egg cells

chromosome

Answer 11

diploid somatic cells /// haploid gamates

Question 12

How many pairs of chromosomes?

chromosome

Answer 12

23 pairs, 22 autosomal, 1 pair sex chromosomes

Question 13

Polyploidy

Answer 13

euploid cell (most cells are dilploid with 46) has some multiple of the normal number of chromosomes; triploidy (three copies) and tetraploidy (four copies of each chromosome) // both conditions are lethal w/ abortion or stillborn, 10% of miscarriages

liver, bronchial, and epithelial => normally polyploid

Question 14

Aneuploidy

chromosome

Answer 14

somatic cells that do not have a multiple of 23 chromosomes; non disjunction (failed to separate)

Question 15

Trisomy (type of aneuploidy)

chromosomes

Answer 15

one chromosome is present w/ 3 copies in somatic cells; partial trisomy is the same with only part of a chromosome (not as detrimental)

trisomy of chromosomes 13, 18, 21 can survive

Question 16

Monosomy (type of aneuploidy)

chromosomes

Answer 16

one chromosome is present in only one copy; lethal

Question 17

chromosomal mosaics

chromosomes

Answer 17

body has two or more genetically different sets of cells in his or her body

Question 18

Down syndrome

chromosomes

Answer 18

Trisomy chromosome 21; IQ 25-70; low nasal bridge, epicanthal folds (monolid), protruding tongue, flat, low set ears.

hypotonia, short stature
* cogential heart defects
* susceptible to respiratory tract infections + leukemia
* By age 40, almost all develop Alzheimer’s because that gene is located on 21

Question 19

Trisomy X (47 XXX)

chromosomes

Answer 19

three X chromosomes; physical abnormalities, sometimes sterility, menstrual irregularlity, or cognitive deficits

flaccid muscles or tall stature

some may even 4 or 5 X chromosomes

Question 20

45 X Karyotype (Turner syndrome)

Answer 20

Presence of single X and no homologous X OR Y ;; always female
* usually sterile
* gonadal streaks rather than ovaries (can be susceptible to cancer in mosaic fetuses w/ cells containing Y chromosome)
* short stature, webbing of the neck, spaced apart nipples
* coarctation (narrowing) of aorta (15-20% cases)
* newborn - edema
* sparse body hair
* spatial and mathematical impairment
* inherit from mother (3/4 cases)

• 15-20% spontaneous abortions; most living individuals are mosaics

Question 21

Treatment for Turner Syndrome patients

chromosomes

Answer 21

Estrogen to develop 2ndary sex characteristics

Question 22

Klinefelter syndrome (47, XXY)

chromosome

Answer 22

at least 2 X chromosomes & a Y chromosome

• male appearance
• sterile usually
• female-like breasts
• testes small, hair sparse, voice high pitched
• stature elevated
• moderate degree mental impairment
• 48 XXXY and 49 XXXXY
• physical and mental impairment increases with each additional X
• mosaic can make it less severe

Question 23

47 XYY karyotype

chromosomes

Answer 23

• taller than avg
• 10-15 pt drop in IQ
• elevated in prison population
• increased incidence of BH d/o

Question 24

cri du chat sydnrome

chromosomes

Answer 24

“cry of the cat” // disease caused by chromosomal deletion in short arm of chromosome 5

• low birth weight
• intellect disability
• microcephaly
• heart defects
• typical facial appearnce (rounded face, widely spaced eyes, a short neck and ears that are positioned low on the head)

Question 25

Duplication

Answer 25

Same part of chromosome repeated, less severe

One example of a rare genetic disorder of duplication is called Pallister Killian syndrome, where part of the #12 chromosome is duplicated (This condition is characterized by extremely weak muscle tone (hypotonia) in infancy and early childhood, intellectual disability, distinctive facial features, sparse hair, areas of unusual skin coloring (pigmentation), and other birth defects.)

Question 26

Inversions

Answer 26

two breaks on chromosomes; followed by reinsertion with inverted order (flip fragment around)

• no apparanet physical effect
• serious problem with offsprings of this inverted person since it can result in duplications or deletions in the chromosomes of the daughter cells

Question 27

Translocations

chromosomes

Answer 27

Interchanging (trading) of genetic materal between nonhomologous chromosomes
Robertsonian translocation are the most clinically significant type (confined to 13, 14 ,15 , 21, 22 b/c they are short arms of these chromosomes and are small w/ no essential genetic material; current person no issues despite only 45 in each cell; their offsprings have serious deletions or duplications

these type of translocations are responsible for 3%-5% of down syndrome cases

Question 28

3 pathways for genetic disease

Transmission of Genetic Diseases

Answer 28

Autosomal dominant, autosomal recessive, x-linked recessive modes of inheritance

Question 29

Pedigree

Transmission of Genetic Diseases

Answer 29

Circle (female), square (male), diamond (not specified)

single parent => no significance
double bar => consanguineous matting (two close relatives)
two lines branching off one middle line making a y-shape (identical twins) - monozygotic
number inside shape (multiple individuals of that SEX)
dark shapes (affected individual)
half colored (autosomal heterozygous recessive) — not affected
dot in middle (carrier)
line diagonal (dead)
SB (stillbirth)

Question 30

Is each birth an independent event (coin toss situation) T/F?

Transmission of Genetic Diseases

Answer 30

True if in case of autosomal domiant or recessive

Question 31

A child can be born with an autosomal disease if neither parent has hx of said disease?

Answer 31

Yes, d/t mutation AND this can happen to multiple offsprings d/t germline mosaicism where a mutation affected all or part of the germline but none of the somatic cells of the embryo; parent can carry this germline change

Germline mutations are changes to your DNA that you inherit from the egg and sperm cells during conception. Somatic mutations are changes to your DNA that happen after conception to cells other than the egg and sperm.

Question 32

Tumor-suppression gene

Transmission of Genetic Diseases

Answer 32

retinoblastoma gene (This gene makes a protein (pRb) that helps stop cells from growing too quickly. Each cell normally has two RB1 genes. As long as a retinal cell has at least one RB1 gene that works as it should, it will not form a retinoblastoma. But when both of the RB1 genes are mutated or missing, a cell can grow unchecked. This can lead to further gene changes, which in turn may cause cells to become cancerous.); normal fx of regulating cell cycle to prevent uncontrollable division; mutation causes lost of such capacity

Inheritable vs noninheritable; autosomal dominant + 1 in 2 chance if one parent has rb1 gene mutation

Question 33

huntington disease

Transmission of Genetic Diseases

Answer 33

autosomal dominant condition // progressive dementia and increasing uncontrollable movements of limbs (chorea) or huntington’s chorea

• age 40 or later (age dependent penetrance)
• affected have children before they know
• if present at birth, many die before reaching reproductive age

Question 34

expressivity

Transmission of Genetic Diseases

Answer 34

extent of variation in phenotype (detectable expression of this genotype – a patient’s clinical presentation.) associated w/ specific genotype

e.g. von Recklinghausen disease - autosomal dominant d/o (type 1 neurofibromatosis)
* involves mutations within the NF1 gene located on chromosome 17 in locus q11. 2 [1,2]. The product of the NF1 gene is neurofibromin and the protein is well known to be a tumor suppressor factor. but sx can vary from harmless spots on skin to malignant tumors, scholiosis, seizures, gliomas (tumor in brain or spinal cord), HTN, learning disabilities, and neuromas (benign growth in nerves)

• a person with mild expression of this gene can pass it onto to their child with severe expression of disease

Question 35

Many autosomal recessive diseases are characterized by (3):

Answer 35

• delayed age of onset
• incomplete penetrance
• variable expressivity

Question 36

For autosomal dominant topic, what applies to generations and parents?

Transmission of Genetic Diseases

Answer 36

Skipped generations are not seen and both male and female are equally likely to exhibit disease

On the other hand, (BONUS)
Autosomal recessive patterns manifest by skipping generations as the affected are usually children of unaffected carriers. It is also common to see affected individuals with unaffected offspring

Question 37

Incomplete penetrance

Answer 37

a gene not always expressed phenotypically

Question 38

Can penetrance be age dependent?

Transmission of Genetic Diseases

Answer 38

Yes such as hungtinton disease and familial breast cancer

Question 39

What if both parents are both heterozygous carriers of recessive gene, what is the recurrence risk for the children?

Transmission of Genetic Diseases

Answer 39

25%

Question 40

Consanguinity

Transmission of Genetic Diseases

Answer 40

Marriage between related individuals; often see in rare diseases (e.g cystic fibrosis)

BONUS
CF sx
Very salty-tasting skin.
Persistent coughing, at times with phlegm.
Frequent lung infections including pneumonia or bronchitis.
Wheezing or shortness of breath.
Poor growth or weight gain in spite of a good appetite.
Frequent greasy, bulky stools or difficulty with bowel movements.
Nasal polyps.

Question 41

Carrier detection tests

Transmission of Genetic Diseases

Answer 41

detect autosomal recessive diseases

Question 42

What happens if first-cousins become partners?

Transmission of Genetic Diseases

Answer 42

frequency of genetic diseases approximately double

Question 43

What happens in each female somatic cell (to the x-chromosome) during embryogenesis?

Transmission of Genetic Diseases

Answer 43

One of 2 x chromosomes inactivate in early embryogenesis

Question 44

X inactivation is ___?

Transmission of Genetic Diseases

Answer 44

random, fixed, and incomplete (only part of chromosome is inactivated)

Question 45

The number of Barr bodies is always ____ than the number of X chromosomes in the cell

Transmission of Genetic Diseases

Answer 45

one less; all but one x chromosome are always inactivaed (e.g for klinefelter w/ XXY then only one Barr body)

Barr body is an inactivated X chromosome in the normal female somatic cell. Inactivation of these chromosomes is known as Lyonization. Lyonization has both genetic and clinical significance. Males do not have barr bodies d/t X+Y

Question 46

How is gender determined embryonically?

Transmission of Genetic Diseases

Answer 46

Presence of SRY gene on Y chromosome (so ulitimately presence of Y); but no SRY gene in Y then an XY female is produced.

An x-chromosome containing SRY gene can produce an XX male

Question 47

X-linked genes

Transmission of Genetic Diseases

Answer 47

Located on x-chromosomes; all known x-linked diseases caused by x-linked recessive gene

Question 48

hemizygous

Transmission of Genetic Diseases

Answer 48

Since males only XY, only one copy of a gene rather than usual two copies

most of the genes of the X chromosome and Y chromosome in human males are hemizygous since males have only one X chromosome (and one Y chromosome) (unlike females that has two X chromosomes).

Question 49

How do x-linked recessive diseases affect males compared to females? Does a father passing to son change anything?

Transmission of Genetic Diseases

Answer 49

Males are more susceptible d/t one copy of gene only; fathers cannot pass x-linked genes to sons

Question 50

Does skipped generations apply to x-linked recessice disease pedigrees?

Transmission of Genetic Diseases

Answer 50

Yes every other generation; carrier females can transmit gene

Question 51

Recurrence risks for x-linked diseases depend on what?

Transmission of Genetic Diseases

Answer 51

Carrier and afflicted status of mother and father (refer to table in google docs for detailed representation)

The last pattern seen is that X-linked recessive traits tend to skip generations, meaning that an affected grandfather will not have an affected son, but could have an affected grandson through his daughter.[4] Explained further, all daughters of an affected man will obtain his mutated X, and will then be either carriers or affected themselves depending on the mother. The resulting sons will either have a 50% chance of being affected (mother is carrier), or 100% chance (mother is affected). It is because of these percentages that we see males more commonly affected than females.

Question 52

Sex-limited trait

Transmission of Genetic Diseases

Answer 52

inherited uterine or testicular defects for example

Question 53

Sex-influenced traits

Transmission of Genetic Diseases

Answer 53

male-pattern baldness for example, more prominent in males but can happen for females hehe

Question 54

Crossing over

Linkage Analysis and Gene Identification

Answer 54

Occurs in meiosis I and causes recombinations of alleles located on the same chromosome pair

Question 55

Marker locus

Linkage Analysis and Gene Identification

Answer 55

closely linked to disease-gene locus, can be used to predict whether an individual will develop a genetic disease