Exam 1 Flashcards
About how many base pairs are their in our genome?
3 billion
What is the makeup of a chromosome?
single double-stranded length of DNA plus proteins
What are the 4 nucleotides and which are paired together?
Adenine with Thymine, guanine with cytosine
How are viruses identified?
Their sequence
In what four locations can a virus enter a cell?
membrane structure, receptors, communication or channels
What four things do you need to test?
a sample with enough material to detect, valid and repeatable test, quick and cheap
What can CRISPR be used for
designing diagnostics and vaccines, cure disease, prevent disease, enhancing human performance, appearance, epigenetic modification, designing new organisms that are more efficient, bioengineering, ecological engineering
Genetics vs. genome
genetics is more general vs. genome is specifics for one organism
Define epigenetics
-where and how we live can affect the accessibility to genes
-this can be passed on
-sequence itself does not change
How are chromosomes ordered
largest to smallest
Define exons
Protein coded genes
Can genes be expressed by a protein?
No
How are bases held together?
Weak hydrogen bonds
How can the bonds that hold bases together come apart?
Heat
Define codons
-Triplet bonds for amino acids
-Corresponds to a tRNA attached to an amino acid or to start or stop
Define translation
-Takes the RNA to proteins
-may be turned up or down
What has a higher mutation rate, single stranded viruses or multi-stranded viruses? Why?
Single because there is nothing to check the strand
Define gene expression
-Gene to protein that affects function
-important because if it is not done correctly , could cause syndromes/disease/conditions such as cystic fibrosis
CNV
-copy number variant- more than 2 copies of one thing
-otherwise known as microdeletions
-less than 5Mb
-too small to see on a karyotype so have to use FISH
-often associated with learning disabilities, speech/language delays, complex phenotype
-occurs when misaligned low copy repeats, for example when a small tip is lost
-common: velocardiofacial (22q11.2 deletion) and Williams (7q11.23)
Do similar complex phenotypes mean similar genetics?
No- think heterogeneity of HL
Why is uracil in RNA but not DNA?
-thymine is more stable in photochemical change and more energetically efficient
-cytosine if damaged loses an amino group which changes it to uracil. a nuclear enzyme identifies these changes and corrects them in DNA
-likely early organisms were RNA based- fast changing, unstable
What are two things that may cause chromosome abnormalities
Meiosis and environmental factors
How often do chromosome abnormalities occur in births
7/1000
What percentage of first semester miscarriages involve chromosome abnormalities
50-70%
What percent of individuals have a chromosome abnormality but their health is not affected? When does this abnormality typically occur?
1%; translocation
How do we know which chromosome is which?
size, centromere and stripes/banding
Karyotype
photograph of a individuals chromosomes
-provides a full view of the nuclear chromosomes and they are identified by banding, fluorescence and size
-need to have live tissues to obtain the chromosome
Which is more specific FISH or a karyotype?
FISH; with a karyotype you do not need a specific hypothesis
Position of telomere
end of chromosome
Position of centromere
“waist” of chromosome
does not have to be in the middle
Chromatin makeup
DNA + proteins
Chromatid
one strand on a duplicated chromosome
What does a cell have to do first prior to meiosis or mitosis
has to be copied
When labeling the arms, what does P mean?
Petite- goes to smallest
Define locus
location of the gene
Does structure affect gene expression
Yes
Heterochromatin
-very condensed
-transcriptionally inactive (turned off)
-centromeres
-may have a repressive effect on nearby genes
-C-G
Does meiosis or mitosis have crossover or recombination
Meiosis
Crossing over
-homologous very precise nothing lost or added
-nonhomologous- site specific
-more of this occurs on bigger chromosomes
-a cellular process that happens during meiosis when chromosomes of the same type of lined up. when two chromosomes (mother and father) line up, parts of the chromosomes can switch. the two chromosomes may contain the same genes but might have different forms of the genes
Recombination
-increases number of different gametes
-each chromosome is a linkage group
-LOD or linkage score
– the farther genes are located from each other on a chromosome, the less likely it is that they will be on the piece that crosses over
– the closer they are, the more likely they are to be separated via crossover
By calculating LOD, what information can be received?
-establish order and distance of genes
-locus of an unknown gene
-hot spots
-sex effects
-a measure of what actually happens
-the farther genes are located from each other on a chromosomes, the less likely it is that they will be on the piece that crosses over
-closer the are, the more they are linked
-can calculate linkage
-log [probability of birth sequence with a given linkage value/probability of birth sequence with no linkage]
Hotspots
where the likelihood of breaking up increases
Polyploidy
a chromosomal number that is a multiple of the normal haploid chromosome set
Aneuploidy
a chromosomal number that is not an exact multiple of the haploid set
Trisomy
-one chromosome having more or less than expected
-except for 13, 18, 21 usually non-viable
-13, 18 are acrocentric (centromere is on top)
-all small chromosomes and active genes less dense
-some can have sex effects
– fewer negative effects
– Turner Syndrome
– Klinefelter (XXY)
–Down Syndrome
Triploidy
-can occur because: errors in meiosis I or II, events in fertilization
-69 chromosomes (3n)
– most common form of this
– high mortality rate
-found in 15-18% of spontaneous abortions
-75% involve two sets of paternal chromosomes
-99% die before brith
Euploidy
normal chromosome number (2n)
Monosomy
-missing a chromosome (2n-1)
-for example 1p36
-clinical characteristics for 1p36: microcephaly, short wide head, deep-set eyes, flat nose and nasal bridge, pointed chin, clefting abnormality in 17%, hypothyroidism in 20%, developmental delay and intellectual disability in 100%, low set ears that rotate back, HL in 82% (mild, HF or HL in about 50% can be CHL or mixed)
-occurs in about 1/5000-1/10000
Turner Syndrome
-80% CHL/mixed, SNHL in adulthood
-45, X
-trisomy’s
Down Syndrome and audiology
-stenotic canals
– wax
– hard to observe TM
– hard to fit HA
– collapsing canals
-ME dysfunction very common
-premature aging of auditory system
Are all meiotic errors harmful?
No!
-some chromosomes stick together
-may have reproductive issues though
-Robertsonian translocation (acrocentric chromsomes- 13, 14, 15, 21, 22)
-common (1/1000)
-balanced
– no excess or deficit of genetic material
– no health issues
Will a chromosomal inversion have any effects?
May have no bad effects
Will a chromosomal deletion have any effects?
Ill effects or not viable
Will a chromosomal duplications have any effects?
may or may not have ill effects
Define transposons
DNA moves from one location to another
Chromosomal deletion versus a microdeletion
microdeletion is less than 35 Mb
What is another term for microdeletions
CNV
Microdeletions
-too small to see on a karyotype (use FISH as an alternative)
-often associated with learning disabilities, speech/language delays, complex phenotype
-occur when misaligned low copy repeats, small tip lost
-ex. Williams
FISH
-Fluorescence in situ hybridization
-a method to identify microdeletions, chromosomal changes
-requires to have a hypothesis
-based on hybridization
-make a small probe and label it with fluoescents
-only useful at the micro level, not useful at the exon level
-needs at least 1000 bases
-does require time to culture the cells
Monosomy 1p36
-most common monosomy microdeletion
-microcephaly, short wide head
-deep set eyes, flat nose and nasal bridge, pointed chin, clefting abnormalities in 17%
-hypothyroidism in 20%
-developmental delay and intellectual disability in 100%
-low set ears rotated back
-HL in 82% (mild, high-frequency or HL in half half these can be CHL or mixed)
Cri du Chat
-5p
-1/20k-50k
-distinct facial features- wide set eyes, low set ears, small jaw
-high pitched cry
-microcephaly
-intellectual disability
-hypoteonia
-cardia issues
-greater risk for ME
-infection
-HL
-ANSD
22q11.2 deletion syndrome
-includes Shprintzen syndrome, DiGeorge, velocardiofacial syndrome
-1/about 4000 but usually de novo (duplication may be 1/1000)
-most common deletion
-can be AD but usually de novo
-Karyotype will be normal but shows up in FISH, CGH and microarray
-ME abnormalities
-learning difficulties, schizophrenia, language delay, artic issues
-microtia, SNHL, CHL, congenital heart disease in 74%, palatal abnormalities in 69%, reduced immune function, calcium metabolism abnormalities, ID
-even if second chromosome is okay, it may not be enough (haploid insufficiency)
De novo
occurs in utero or before (no parental inheritance)
Williams Syndrome
-typically de novo
-microdeletion syndrome
1/20,000
-24 genes including elastin ELN
-strong social and verbal skills, ID especially in the visuospatial processing area, facial abnormalities, cardiac issues, phonophobia
-HF HL
-acoustic reflexes will be decreased or absent
Haploid insuffiency
-need both alleles to produce enough for full function
-phenotypically dominant autosomal
Mosaicism
-a complication both chromosome and single base have
-one zygote, genetic change overtime
-2 zygote fuse in utero
How are females a mosaic?
X chromosome are inactive; 1 x in every cell is randomly turned off
Is imprinting parental specific? Give an example
Yes. Angelman and Prader-Willi is an example where Prader is on the paternal and Angelman is the maternal
Uniparental disomy
2 copies from 1 parent
Choanal atresia
block in the nose usually associated with CHARGE syndrome
VUS
variants of unknown significance
Give an example of an STR (short tandem repeats)
Huntingtons Disease
What can break hydrogen bonds that hold the nucleotides together?
heat
Describe hybridization and dematuration
-dematuration involves the DNA strands separating
-hybridization involves the strands coming back together
-if the strands do not come back together perfectly, then it is not as stable
Oligo
many pieces but smaller bases
What does the peak size represent for Sanger sequencing?
how many copies of the gene exist
If there are two bases in one spot for Sanger sequencing, what is that called?
heterozygous
How is PCR data organized?
by size, it will show if there are multiple copies
MLPA
-2 primers with a small space that will identify a few bases
-if there is too much DNA? the test cannot be completed
-this is a good way to look at small deletions or multiplications
-another way to look at copy number variant as small as a single exon by using two specific probes that flank the area of interest which is filled in by a specific enzyme and the resulting linked piece of DNA is amplified and comapred to control (if exon is missing, the nonlinked probes are not amplified
