Unit 2 Pathophysiology - Chapter 4 Genes and Genetic Diseases Flashcards
DNA - four nitogenous bases
DNA, RNA, and Proteins: Heredity at the Molecular Level
adenine, cytosine, guanine, thymine [uracil - RNA]
DNA polymerase
DNA, RNA, and Proteins: Heredity at the Molecular Level
replication; adds bases to new strand, performs proofreading fx
Mutation
DNA, RNA, and Proteins: Heredity at the Molecular Level
inherited alteration of genetic material
Mutagens
DNA, RNA, and Proteins: Heredity at the Molecular Level
substances that causes mutations; radiation, chemicals (nitrogen mustard, vinyl chloride, alkylating agents, formaldehyde, sodium nitrate)
nitrogen mustard strongest while sodium nitrate weakess
Phenylketonuria
DNA, RNA, and Proteins: Heredity at the Molecular Level
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.
Transcription
process by which DNA specifies a sequence of mRNA.
transcription is to make a RNA copy of a gene’s DNA sequence.
Introns vs exons
process by which DNA specifies a sequence of mRNA.
Excised seqeunces vs remaining strand for coding of proteins
MicroRNAs (miRNAs)
7 to 27 nucleotides in length, that bind to specific mRNA sequences and down-regulate their expression.
long noncoding RNA (lncRNA)
process by which DNA specifies a sequence of mRNA.
greater than 200 nucleotides; a non translated RNA => genome contains 10,000 lncRNA and can be involved in gene regulation
Translation
process by which DNA specifies a sequence of mRNA.
RNA directs synthesis of polypeptides (takes place in ribosome)
Body cells? Sperm + egg cells
chromosome
diploid somatic cells /// haploid gamates
How many pairs of chromosomes?
chromosome
23 pairs, 22 autosomal, 1 pair sex chromosomes
Polyploidy
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
Aneuploidy
chromosome
somatic cells that do not have a multiple of 23 chromosomes; non disjunction (failed to separate)
Trisomy (type of aneuploidy)
chromosomes
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
Monosomy (type of aneuploidy)
chromosomes
one chromosome is present in only one copy; lethal
chromosomal mosaics
chromosomes
body has two or more genetically different sets of cells in his or her body
Down syndrome
chromosomes
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
Trisomy X (47 XXX)
chromosomes
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
45 X Karyotype (Turner syndrome)
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
Treatment for Turner Syndrome patients
chromosomes
Estrogen to develop 2ndary sex characteristics
Klinefelter syndrome (47, XXY)
chromosome
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
47 XYY karyotype
chromosomes
- taller than avg
- 10-15 pt drop in IQ
- elevated in prison population
- increased incidence of BH d/o
cri du chat sydnrome
chromosomes
“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)
Duplication
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.)
Inversions
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
Translocations
chromosomes
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
3 pathways for genetic disease
Transmission of Genetic Diseases
Autosomal dominant, autosomal recessive, x-linked recessive modes of inheritance
Pedigree
Transmission of Genetic Diseases
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)
Is each birth an independent event (coin toss situation) T/F?
Transmission of Genetic Diseases
True if in case of autosomal domiant or recessive
A child can be born with an autosomal disease if neither parent has hx of said disease?
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.
Tumor-suppression gene
Transmission of Genetic Diseases
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
huntington disease
Transmission of Genetic Diseases
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
expressivity
Transmission of Genetic Diseases
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
Many autosomal recessive diseases are characterized by (3):
- delayed age of onset
- incomplete penetrance
- variable expressivity
For autosomal dominant topic, what applies to generations and parents?
Transmission of Genetic Diseases
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
Incomplete penetrance
a gene not always expressed phenotypically
Can penetrance be age dependent?
Transmission of Genetic Diseases
Yes such as hungtinton disease and familial breast cancer
What if both parents are both heterozygous carriers of recessive gene, what is the recurrence risk for the children?
Transmission of Genetic Diseases
25%
Consanguinity
Transmission of Genetic Diseases
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.
Carrier detection tests
Transmission of Genetic Diseases
detect autosomal recessive diseases
What happens if first-cousins become partners?
Transmission of Genetic Diseases
frequency of genetic diseases approximately double
What happens in each female somatic cell (to the x-chromosome) during embryogenesis?
Transmission of Genetic Diseases
One of 2 x chromosomes inactivate in early embryogenesis
X inactivation is ___?
Transmission of Genetic Diseases
random, fixed, and incomplete (only part of chromosome is inactivated)
The number of Barr bodies is always ____ than the number of X chromosomes in the cell
Transmission of Genetic Diseases
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
How is gender determined embryonically?
Transmission of Genetic Diseases
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
X-linked genes
Transmission of Genetic Diseases
Located on x-chromosomes; all known x-linked diseases caused by x-linked recessive gene
hemizygous
Transmission of Genetic Diseases
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).
How do x-linked recessive diseases affect males compared to females? Does a father passing to son change anything?
Transmission of Genetic Diseases
Males are more susceptible d/t one copy of gene only; fathers cannot pass x-linked genes to sons
Does skipped generations apply to x-linked recessice disease pedigrees?
Transmission of Genetic Diseases
Yes every other generation; carrier females can transmit gene
Recurrence risks for x-linked diseases depend on what?
Transmission of Genetic Diseases
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.
Sex-limited trait
Transmission of Genetic Diseases
inherited uterine or testicular defects for example
Sex-influenced traits
Transmission of Genetic Diseases
male-pattern baldness for example, more prominent in males but can happen for females hehe
Crossing over
Linkage Analysis and Gene Identification
Occurs in meiosis I and causes recombinations of alleles located on the same chromosome pair
Marker locus
Linkage Analysis and Gene Identification
closely linked to disease-gene locus, can be used to predict whether an individual will develop a genetic disease
