Introduction and Genetics Flashcards
Pathophyisology
derangement of function seen in disease
Disease
a condition with signs or symptoms that is linked to an increased risk of future death or disability
symptom
a subjective indication of a disease reported by a patient
sign
an objectively observed phenomena associated with disease
three examples of signs
- blood work
- x rays
- physical examination
three examples of symptoms
- nausea
- pain
- fatigue
genetics
the study of heredity and its variations
heredity
the passing of traits to offspring from parents or ancestors
gene
a molecular unit of inheritance
what are the four DNA nucleotides
- adenine
- guanine
- cytosine
- thymine
central dogma of genetics (4)
- DNA unzips to form a template for mRNA
- mRNA leaves the nucleus and proceeds to ribosomes
- tRNA carries amino acids to ribosomes
- proteins are constructed using mRNA as a template
exons
segments of DNA which code for mRNA used in protein synthesis
introns
segments of DNA which code for RNA but not protein synthesis
genome
the entire DNA sequence of an indvidual
exome
the 1.5-2% of which are exons that encode proteins
what determines genetic diversity between individual and species
the non-coding genome
what percent of disease causing mutations are found in the exome? the non-exome?
- 60-65%
- 35-40%
what are the two parts that make up condense chromatin
DNA + proteins
what are the four functions of chromosomes
- packaging
- protection
- progeny
- programming
why are chromosomes important for packaging
the coiling of the chromosome allows for 2m of chromatin to fit in the nucleus
two types of chromosome proteins
- Histone
- Non-histone
what is the function of histone proteins
encourages coiling and supercoiling of chromatin
how many types of histone proteins are there
5
what do non-histone proteins do
regulate transcription, replication, repair, and recombination of DNA
what is the difference between an autosome and sex chromosome
sex chromosomes determine gender and sex linked traits, autosomes are any other chromosome
what are the two arms of chromosomes called
p and q arms
what is the difference between the p and q arms of a chromosome
p is short, q is long
how many chromosomes do humans normally have
46, 23 pairs, one from each parent
where else can DNA normally be found in the cell
mitochondria
what is the composition of the mitochondrial genome
circular DNA consisting of 13 protein genes and 24 RNA only genes
from what parent does an offspring receive mitochondrial DNA
the mother
what three types of cells undergo mitosis
- somatic
- germ
- neoplastic
what cells undergo meiosis
specialized cells from the germ line
what are the two distinctions of meiosis from mitosis
- crossing over occurs in metaphase I
- the second meiotic division produces haploid cells
what is the male cell that undergoes meiosis? how many spermatozoa are produced
- primary spermatocyte
- 4 spermatozoa
what female cell undergoes meiosis? what is the product?
- primary oocyte
- 1 matiure ovum and 2 polar bodies
A) cumulus oopharus
B) zona pellucida
C) chromosomes
D) first polar body
cytogenetics
the branch of genetics concerned with the relationship of chromosome structure and function to disease
polyploidy
involving multiple copies of chromosomes
aneuploidy
a state in which a cell has an abnormal number of chromosomes
three examples of abnormalities in chromosome structure
- deletions
- translocations
- inversions
T/F aneuploid cells can be plus or minus chromosomes
true
in general what is worse, having too many chromosomes or not enough?
in generally missing chromosomes are more harmful than extra chromosomes
what are two causes of polyploidy
- polyspermia
- failure to expel a polar body
are there any clinical risk factors that lead to polyspermia
none that have been identified
what is a typical cause of aneuploidy in gametes
nondisjunction during meoisis I, anaphase lag
how often does aneuploidy occur
it occurs sporadically, but it happens more often in older oocytes
what is the result of nondisjunction
two gametes produced are n-1, two gametes are n+1
how often do spontaneous abortions/miscarriage occur
10-20% of clinical pregnancies
when do more miscarriages happen
within the first trimester (14 weeks)
what is a factor that can increase the incidence of a miscarriage
increased age of the mother
what is commonly found in 50-60% of spontaneously aborted embryos
major cytogenic abnormalities (polyploid, monosomy, trisomy)
in what two circumstances will aneuploidy produce lethal defects
- autosomal monosomy
- monosomy Y
what circumstance will allow the survival of an aneuploid embryo
monosomy X, results in turners syndrome
Will an embryo with autosomal trisomy produce a viable fetus?
usually not, only if the trisomy is in chromosomes 13, 18, or 21
turners syndrome
an aneuploid X condition, resulting in a single X female
what is the phenotype displayed in turner syndrome
a short female with a webbed neck and shield chest
what are four special problems related to turners syndrome
- amenorrhea/infertility
- kidney malformations
- congenital heart disease
- aortic arch dilation and rupture
what is a sign of turner syndrome commonly seen at birth
swollen hands and feet from lymphadema
what is a result of trisomy 21
down syndrome
what is the phenotype displayed in trisomy 21
a male or female with slanted eyes, a flat nose, small chin, and protruding tongue
what are three risks associated with trisomy 21
- mental retardation
- increased risk of many medical conditions
- accelerated aging
what are four medical conditions that are more common with down snydrome
- congenital heart disease
- cataracts
- seizures
- alzheimers
what are two other trisomys besides 21 that produce offspring
trisomy 18 and trisomy 13
what is the result of Trisomy 18
severe physical defects and a markedly decreased lifespan
what are four conditions present with trisomy 13
- microcephaly
- cleft lip and palate
- ambiguous genitalia
- shortened lifespan
what is another name for trisomy 18? trisomy 13?
- edwards syndrome
- patau syndrome
Robertsonian translocation
when the q and p arms of a chromosome become switched to produce a chromosome with two q arms and one with 2 p arms
two main modes of inheritance
- mendelian
- multifactorial
mendels laws (4)
- traits are the results of genes
- genes come in pairs, 1 paternal 1 maternal
- genes come in variations (alleles)
- genes are inherited separately from other genes
what are four revisions to mendels laws
- codominance
- incomplete pentrance
- genes are on chromosomes
- genes can be linked
what is an example of incomplete penetrance
polydactylism
four types of mendelian transmission
- autosomal dominant
- autosomal recessive
- sex linked dominant
- sex linked recessive
when is a situation when heterozygosity is advantageous
when having a recessive trait that can be passed on or partially expressed increases survival, like sickle cell disease
when would you suspect that a heterozygousity is advantagoes
when there are a lot of heterozygotes in the population
what can blunt the effect of a mutation in a dominant gene
action of other genes
what significantly increases the occurance of recessive mutation
inbreeding
T/F disorders caused by recessive mutations are more common in older parents
false, dominant mutations are more likely
when would the supposed cause of a genetic disease be an autosomal dominant gene
- disease doesn’t skip generation
- affects males and females equally
- 50% chance of transmission
when would you suspect an autosomal recessive cause of a disease
- when it disease can skip generations
- both genders equally affected
- 25% chance for affected or normal, 50% for carrier
when would a disease be suspected to have an x linked dominant cause
- when an affected female can pass on affliction to both genders
- an affected male will always pass the affliction to daughers
when would an x linked recessive trait be linked to disease
- affect fathers produce carrier daughters
- affected mothers have a 1/4 chance of a carrier daughter and a 1/4 chance of an afflicted son
why are x linked recessive disease more common in males
because females have a second X gene that can make up for the mutated X
four principles used to analyze pedigree
- is the disease common or rare
- does the gene skip generations
- gender ratio of afflicted persons
- are there gender limits to transmission
what would no male to male transmission indicate
the gene is X linked in the father, because males don’t pass their X gene to sons
why is the number of afflicted people relevant to pedigree analysis
because autosomal diseases are more common than X linked
why is generation skipping relevant to pedigree analysis
because dominant traits don’t skip generations
what is the likelihood of an afflicted child born to parents who both have the same autosomal condition
3/4
what is the ratio for a dihybrid cross with heterozygous parents
- 9 are normal
- 3 are homozygous for one gene
- 3 are homozygous for the other
- 1 is homozygous for both
in what type of genetic disorder does the mother pass on the disease 100% of the time? why
mitochondrial disease, because all the mitochondrial DNA is always 100% maternal
what are four common symptoms of mitochondrial disease
- encephalopathy
- myopathy
- loss of senses
- lactic acidosis
what would be suspected when there is a genetic disease present with no known family history
random mutation
what are two synonyms for multifactorial inheritance
polygenic inheritance
quantitative inheritance
examples of continuous characteristics
height
skin color
intelligence
what two types of genetic disease are caused by multifactorial traits
- congenital disease
- adult onset disease
what increase the risk of having a congenital or adult onset disease
the number of affected individuals in the family and how severe the defect is
T/F most congential and adult onset genetic disorders have afflicted parents
false, most have normal
four examples of congenital disorders with multifactorial inheritance
- cleft palate
- congenital heart disease
- neural tube deficits
- pyloric stenosis
for congenital orders, what is the recurrence risk with one affected family member? two?
3%
9%
3 examples of adult onset multifactorial disease
- diabetes
- cancer
- epilepsy
how much does the risk of an adult onset disease increase with one relative
it doubles
what is the jacob-monod model of gene expression
a regulator gene upstream controls an operator gene, which in turn controls a structural gene with a repressor protein
the repressor will bind to the operator to block expression, or bind with a substrate if expression is needed
T/F non-coding RNA can regulate DNA expression
true, they can act as repressors or activators
riboswitch RNA
an RNA strand that, when not activated, blocks the translation of a protein coding mRNA
activation forces a confirmation change that frees the mRNA for transcription
RNA interference
a method of silencing gene expression with short RNA strands binding to mRNA
two molecules responsible for mRNA interference
- micro RNA
- small interfering RNA
what is micro RNA and how does it limit gene expression
small segment of non coding RNA
affects the action of mRNA by degradation or blocking ribosomal attachment
two general options for gene therapy
- insert a normal gene into a genome with a mutated gene
- turn off transcriptions of bad genes and turn on transcription of good genes
how is gene therapy used to treat hemophilia A
siRNA directed against anticoagulant antithrombin III reduces the production of antithrombin II, which increases the bloods ability to clot
epigenetics
heritable changes not cased by changes in DNA sequence
three examples of epigenetic regulation
- genomic imprinting
- histone spool regulation
- x chromosome inactivation
genomic imprinting
when one allele for a gene is silenced through methylation
how can a recessive genetic disorder be made to look like a dominant disorder
with genomic imprinting, if the dominant normal allele has been silenced the mutated recessive allele will be expressed
histone control/code
the pattern of chemical attachments to histone spools make genes more or less likely to be expressed based on what DNA is wrapped around the histone
what does alternative splicing do
allows for the production of significantly more proteins to be produced from the same genetic material
splicosome
the enzyme responsible for splicing out RNA segments
what are two examples of organisms with mixed genomes
- mosaics
- chimeras
mosaicism
two more more cell lines with different genotypes in one organism, descended from one fertilized egg
what causes mosaicism
a mutation early indevelopment that produces a slightly different genome
why is female mosaicism considered normal
because one of the females X genes is deactivated randomly, and during development that can give rise to cells with different X genes activated
chimera
an individual with two or more cell lines derived from different zygotes
how common are true chimeras? what is the usual cause
extremely rare
abnormal embryo development and fusion of fraternal twins
what are three causes of mutation
- spontaneous DNA regulation
- replication errors
- environmental factors
how frequent to replication errors occur?
after repair mechanisms, how many errors in the genome are actually present
1 copy error for every 10 million base pairs
3-4 errors per genome copy
what are four examples of enviromental factors that cause mutataions
- free radicals
- radiation
- chemotheraputic drugs
- natural DNA toxins
two possible locations for mutations
which are cause heritable mutation
somatic or germ cells
only germ cell mutations are heritable
what are the two metabolic consequences of mutations
which can cause neoplasia
loss or gain of function
either can lead to neoplasia
four types of DNA mutations
- silent
- missense
- nonsense
- frameshift
how can mutations be silent
because the protein code is redundant, some times a change in codon doesn’t change the amino acid, or the changed amino acid doens;t change the protein
SNP
single nucleotide polymorphism, a change in one nucleotide
missense mutation
when a SNP doesn;t results in the production of a different protein by changing one amino acid
nonsense mutation
when a codon is changed to a stop codon
frameshift mutation
when there is a deletion or addition that changes the DNA by a multiple other than three, all the codons downstream are changed
tumor suppressor genes
genes that repress the function of cell division genes and keep cells from dividing
