Exam 1 Flashcards
1
Q
About how many base pairs are their in our genome?
A
3 billion
2
Q
What is the makeup of a chromosome?
A
single double-stranded length of DNA plus proteins
3
Q
What are the 4 nucleotides and which are paired together?
A
Adenine with Thymine, guanine with cytosine
4
Q
How are viruses identified?
A
Their sequence
5
Q
In what four locations can a virus enter a cell?
A
membrane structure, receptors, communication or channels
6
Q
What four things do you need to test?
A
a sample with enough material to detect, valid and repeatable test, quick and cheap
7
Q
What can CRISPR be used for
A
designing diagnostics and vaccines, cure disease, prevent disease, enhancing human performance, appearance, epigenetic modification, designing new organisms that are more efficient, bioengineering, ecological engineering
8
Q
Genetics vs. genome
A
genetics is more general vs. genome is specifics for one organism
9
Q
Define epigenetics
A
-where and how we live can affect the accessibility to genes
-this can be passed on
-sequence itself does not change
10
Q
How are chromosomes ordered
A
largest to smallest
11
Q
Define exons
A
Protein coded genes
12
Q
Can genes be expressed by a protein?
A
No
13
Q
How are bases held together?
A
Weak hydrogen bonds
14
Q
How can the bonds that hold bases together come apart?
A
Heat
15
Q
Define codons
A
-Triplet bonds for amino acids
-Corresponds to a tRNA attached to an amino acid or to start or stop
16
Q
Define translation
A
-Takes the RNA to proteins
-may be turned up or down
17
Q
What has a higher mutation rate, single stranded viruses or multi-stranded viruses? Why?
A
Single because there is nothing to check the strand
18
Q
Define gene expression
A
-Gene to protein that affects function
-important because if it is not done correctly , could cause syndromes/disease/conditions such as cystic fibrosis
19
Q
CNV
A
-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)
20
Q
Do similar complex phenotypes mean similar genetics?
A
No- think heterogeneity of HL
21
Q
Why is uracil in RNA but not DNA?
A
-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
22
Q
What are two things that may cause chromosome abnormalities
A
Meiosis and environmental factors
23
Q
How often do chromosome abnormalities occur in births
A
7/1000
24
Q
What percentage of first semester miscarriages involve chromosome abnormalities
A
50-70%
25
What percent of individuals have a chromosome abnormality but their health is not affected? When does this abnormality typically occur?
1%; translocation
26
How do we know which chromosome is which?
size, centromere and stripes/banding
27
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
28
Which is more specific FISH or a karyotype?
FISH; with a karyotype you do not need a specific hypothesis
29
Position of telomere
end of chromosome
30
Position of centromere
"waist" of chromosome
does not have to be in the middle
31
Chromatin makeup
DNA + proteins
32
Chromatid
one strand on a duplicated chromosome
33
What does a cell have to do first prior to meiosis or mitosis
has to be copied
34
When labeling the arms, what does P mean?
Petite- goes to smallest
35
Define locus
location of the gene
36
Does structure affect gene expression
Yes
37
Heterochromatin
-very condensed
-transcriptionally inactive (turned off)
-centromeres
-may have a repressive effect on nearby genes
-C-G
38
Does meiosis or mitosis have crossover or recombination
Meiosis
39
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
40
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
41
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]
42
Hotspots
where the likelihood of breaking up increases
43
Polyploidy
a chromosomal number that is a multiple of the normal haploid chromosome set
44
Aneuploidy
a chromosomal number that is not an exact multiple of the haploid set
45
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
46
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
47
Euploidy
normal chromosome number (2n)
48
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
49
Turner Syndrome
-80% CHL/mixed, SNHL in adulthood
-45, X
-trisomy's
50
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
51
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
52
Will a chromosomal inversion have any effects?
May have no bad effects
53
Will a chromosomal deletion have any effects?
Ill effects or not viable
54
Will a chromosomal duplications have any effects?
may or may not have ill effects
55
Define transposons
DNA moves from one location to another
56
Chromosomal deletion versus a microdeletion
microdeletion is less than 35 Mb
57
What is another term for microdeletions
CNV
58
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
59
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
60
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)
61
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
62
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)
63
De novo
occurs in utero or before (no parental inheritance)
64
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
65
Haploid insuffiency
-need both alleles to produce enough for full function
-phenotypically dominant autosomal
66
Mosaicism
-a complication both chromosome and single base have
-one zygote, genetic change overtime
-2 zygote fuse in utero
67
How are females a mosaic?
X chromosome are inactive; 1 x in every cell is randomly turned off
68
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
69
Uniparental disomy
2 copies from 1 parent
70
Choanal atresia
block in the nose usually associated with CHARGE syndrome
71
VUS
variants of unknown significance
72
Give an example of an STR (short tandem repeats)
Huntingtons Disease
73
What can break hydrogen bonds that hold the nucleotides together?
heat
74
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
75
Oligo
many pieces but smaller bases
76
What does the peak size represent for Sanger sequencing?
how many copies of the gene exist
77
If there are two bases in one spot for Sanger sequencing, what is that called?
heterozygous
78
How is PCR data organized?
by size, it will show if there are multiple copies
79
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
80
Is dystrophin more common in men or women?
Men because it is x-linked and therefore inly one copy of the gene is needed to express it
81
What deletion is Prader-Willi/Angelmen syndromes
15q11-q13
82
Prader-Willi Syndrome
-paternal chromosome deletion at 15q11-13
-sporadic
-maternal copy is turned off by imprinting
-obesity
-intense craving for food
-hypotonia
-mild ID
-hypogonadism
83
Angelman Syndrome
-deletion on maternal chromosome 15q11-13
-non-functional paternally inherited UBE3A gene in the brain
-severe developmental delay
-absent or nearly absent speech
-ataxia
-microcephaly
-seizures
-hypermotoric activity
-drooling
-sleep disturbances
-attraction to or fascination with water
-feeding problems
-happy demeanor
-excitable personality
84
Barker hypothesis
intrauterine experience affects lifelong metabolism
85
Chromatin diseases
-ex. Rett syndrome
86
CHARGE syndrome
-coloboma
-heart defect
-choanal atresia
-delayed growth and development
-genital abnormality
-ear abnormality
-considered dual sensory impairment
-8q12.2
-CHD7 gene in 50% of cases
-chromatin remodeling protein
-1/8500-1/10000
-SCC hypoplasia/agenesis 95%+
-HL, variable severity
-external ear is often asymmetric
-cochlear nerve deficiency with atresia of the cochlear aperture, abnormalities of cochlear partitioning, and anomalies of cranial nerves
-CI have various success
-delayed postural development
ear defects are usually bilateral
87
Knockdown
-a way to interfere with gene expression (prevent or alter translation)
88
Translocation
-How RNA gets out of the nucleus to the cells
-changes in chromosome structure or content
-reciprocal translocation
-robertsonian translocations
89
How may exons does GJB2 have?
2
90
Isoforms
some gene product in a big picture with a few exception
91
Mutants (variants)
-heritable changes in genotype
-change in DNA base sequence
-affects phenotype
-may be conditional
-single base pair change (may be from UV, mutagens, spontaneous changes)
-multiple base pair changes
-repeats CNV
-chromosomal
-heritable change in genotype, change in DNA base sequence, affects phenotype, may be conditional
92
Missense mutation
-change in a base, typically change in one base
-codons are not changes
-not pathogenetic
93
Frameshifts- what type of mutation are they usually? When are frameshifts bad?
-Usually nonsense mutation
pIf they are in a group of 2 or 3, it is okay but if they are in a group of four... bad
-In general, they are bad
-a mutation caused by the addition or deletion of a base pair or base pairs in the DNA of a gene resulting in the translation of the genetic code in an unnatural reading frame from the position of the mutation to the end of the gene
94
Addition/deletion with type of mutation
-if out of frame, will be a nonsense mutation
-if in frame, will be missense
95
What type of mutation is a substitution change?
Missense
96
Truncating
Protein is cut short; frameshift
97
Nontruncating
Missense, get entire gene expression but will not work well
98
Loss of function
-Usually wild type
-AR
-usually enough for function, but if not that is called haploinsufficiency
-refers to genetic mutations that lead to the reduction or loss of the normal function of a gene or its product
-may affect proteins or structures critical for hearing
99
Gain of fucntion
-does something difference than original
-AD
-refers to genetic mutations that result in the gene acquiring new, abnormal function or becoming overactive
-can disrupt the normal functioning of the auditory system
-associated with an AD mutation
100
Family linkage
-mendelian diseases
-less useful for multifactorial
-need big families
-families share lots of genes
-1st AD HL gene- Costa Rica
101
Candidate gene
-gene believed to influence expression of complex phenotypes due to known biological and/or physiological properties of its products, or to its location near a region of association or linkage
-identify likely genes
-need to understand relationships, pathways
-expensive, limited number
102
Bioinformatics
-know what genes look like or know what functions might affect and work backward
103
GWAS
-genome-wide associated studies
-complex, non-mendelian diseases
- high through-put genotyping technology
-SNP assay
-relate to disease/traits
-not hypothesis driven
-danger of false positives
104
Nonsyndromi loci: DF
deafness gene
105
Nonsyndromi loci: DFN, DFNX
x-linked deafness gene
106
Nonsyndromi loci: DFNA
dominant deafness gene
107
Nonsyndromi loci: DFNB
recessive deafness gene
108
DFNM
modifier
109
FISH
-requires you to have a hypothesis
-based on hybridization
-make a small probe and label it with fluorescent manner
-only useful at microlevel
110
Mitochondrial
-transferred from mother to all children
-can be later onset and variable
111
SNPs (single nucleotide polymorphism)
-very stable
-not typically going to change phenotype
-unusual to change gene function
-used as markers because with specific genetic makeup
-one single polymorphism
-genetic variant that occurs at the level of about 1% or more of the population
-may affect gene function
-most occur between genes so there will be no effect
-role in identification of genes that cause HL
-can help with the diagnosis and prediction of disease and disease susceptibility, ancestry
112
Haplotype
family of SNPs traveling together
-imply that they are going to be specific alleles that travel together
-not specific but somewhat predictable
-a group of specific alleles at neighboring genes or markers that tends to be inherited together
113
Phenotype
physical expression of a gene
114
Chromosome
long thread-like structure made of DNA and associated proteins (histones)
115
Meiosis
-going from 2n to 1n, this happens only in gametes, results in diverse outcomes
-not all errors are harmful (about 1 in 1000 are not)
-sometimes they are balanced- so no excess or deficit of genetic material and no health difficulties
116
Mitosis
-occurs in somatic cells
-one cell division resulting in two daughter cells
-chromosome number per nucleus is maintained
-one premeiotic S phase per cell division
-normally no pairing of homologs and no crossover
-centromeres divide at anaphase
-conservative process- daughter cells genotypes are identical with parental genotypes
-cells undergoing mitosis can be diploid or haploid
117
Alternative splicing
process of generating multiple mRNA molecules from a given set of exons from the primary transcript to form mature mRNAs
118
Replication
the copying of information or genes
119
Transcription
synthesis of RNA to DNA
120
Translation
-makes a protein
-ribosomes attached to the end of the mRNA, moves along the sequence until it picks up the start codon. incorporates amino acids based on what the codons are coding into the polypeptide chain it is making until it reaches stop codon. ribosome falls off mRNA, protein must be folded correctly
-changes that occur during translation (one form of Charcot Marie Tooth, several mitochondrial syndromes, enzymes that affect end point protein structure
121
Recombination
increases the number of different gametes, each chromosome is a linkage group
122
Gene expression
-gene to protein that affects
-process by which the information is encoded
123
Proteome
complete set of proteins expressed by an organism, cell or tissue
124
Polymorphism
benign single base change
125
Point mutation
a mutation affecting only one or very few nucleotides in a gene sequence
126
Allele
alternate forms of a gene which occupy the same locus on homologous chromosomes
127
Base
-same thing as a nucleotide
-4 different options: adenine, thymine, guanine and cytosine
128
Histone
protein that the DNA wraps around
129
Methylation
-adds a chemical group to specific places on the DNA where it then blocks the proteins that attach tp DNA to read the gene
-this chemical group can be removed through demethylation
-methylation turns genes on and demethylation turns genes off
130
What are 3 regulatory RNAs? What are there primary purpose?
-miRNA: micro
-siRNA: small interfering
-snoRNA: small nucleolar
-affect gene expression
131
What are the two things chromatin is made out of?
DNA + proteins
132
Diploid
-a diploid karyotype is 46 chromosomes because there are two copies of each chromosome
-one inherited from each parent
133
Dominant
-only need one of the gene to be expressed
134
Recessive
-double dose of gene required
-chance of offspring having it is 25%
-carrier parents
-horizontal family pattern
-usually complete penetrance and expressivity
135
Nonsense mutation
frameshift
addition
deletion
136
Insertion
addition of one or more nucleotides base pairs to a DNA sequence
137
Intron
-a region that resides within a gene but does not remain in the final mature mRNA molecule following transcription of that gene and does not code for amino acids that make up the protein encoded by that gene
-most protein coding genes in the human genome consist of introns and exons
138
Promoter
-region of DNA that initiates transcription of a particular gene
-must be present in the gene for it to work
-if the promoter was to turn off, this would turn the gene off/make it unproductive
139
Isoform
some gene product in a big picture with a few exceptions
140
DNA polymerase
-adds nucleotides
-goes in a specific direction (adds to 3 prime)
141
Polymerase chain reaction (PCR)
making lots of copies but only of the section of DNA that follows primers
142
Syndrome
-group of symptoms or traits that occur together can cause a specific disease
-can come from: chromosomal abnormality, regulatory genes, infection, environmental/chemical changes
143
Heteromeric
-differ in the transfer of larger molecules (cx 26 and cx30)
-a gap junction channel composed of two or more different types of connexin
-show faster intracellular ca2+ signaling than homoeric counterparts
-Cx26 can make up for a lack of cx30 but not vice versa
144
Homomeric
gap junction made of a single connexin protein
145
Connexon
involved in forming gap junctions, which facilitate direct cell-to-cell communications
146
Gap junction
passage of ions and small molecules, regulation
147
Digenic
2 different loci (ex. 2 genes that specify proteins that interact, possible variable expressivity, rare)
148
Biallelic
2 copies with one on each allele
149
Wild type
normal
150
Interactome
representation of functional interactions between molecules
151
Penetrance
the extent to which a particular gene or set of genes is expressed in the phenotype pf the individuals carrying it
152
Expressivity
the degree to which a genotype is expressed as a phenotype in an individual
153
Heterogeneity
when different genetic mechanisms or gene mutations cause the same or similar disease or condition
154
Polygenic
determined by more than one gene
155
Mosaicism
-complication both chromosomal and single base
-men may lose Y chromosome in some cells which makes them at higher risk for heart disease
-clonoal hematopoiesis increases in some cells which makes them higher risk for heart disease
-females are mosaic- for XX, both chromosomes can be active but one X can be deactivated by epigenetic process at random
156
X inactivation
this is what causes mosaicsim die to one X being randomly inactivated
157
Imprinting
-sometimes genes from a paternal or maternal source are unactivated preferentially ex. Prader-Willi/Angelman
-an example of normal epigenetics but genes are expressed differentially based on the origin
158
Uniparental disomy
both members of the chromosome pair are inherited from one parent ex. Prader-Willi/Angelman
159
Multifactorial
determined by one or more genes as well as the environment
160
Phenocopy
change in phenotype during development usually due to environmental factors, it will show a characteristic genotype that is not its own
161
Sanger sequencing
-chain termination method
-cannot do entire chromosome so need to fragment DNA
-considered the gold standard
162
35delG
-GJB2 mutation that is more common in Caucasian population
-frameshift that is truncating
-results in a stop codon
163
167delT
GJB2 mutation that is more common in Caucasian Ashkenazi Jewish population
164
235delC
GJB2 mutation common in Southeast Asian population
165
V37I
GJB2 allele most common in Asia
166
M34T
GJB2 gene that is AR and nonsyndromic HL, severity can vary
167
R143W
GJB2 mutation, more common in some parts of Africa
168
MLPA
-type of PCR that enables amplification of multiple targeted sections of DNA
-can detect small deletions and duplication
-can detect single exon deletions or duplications
168
GJB2 microdeletions and duplication
-many microdeletions can be found on chromosome 13
-duplications are less common but can happen ex. exon 1 duplication which can have HL:
169
CGH
-can detect trisomies, deletions, duplications, microdeletions, unbalanced translocations
-physical panel that has panel that tests for things
-cannot pick up single exons
170
Quantitative PCR
-can check the number of exons or repeats
-uses primer labeled with fluoescence PCR
-results are sorted for each pf the 2 chromosomes by size
171
NGS (next generation sequencing)
-can help diagnose HL from mutations of GJB2
-it is a faster test and more cost effective
172
MPS (massively parallel sequencing)
same as NGS (can help to diagnose HL from mutations of GJB2; it is faster and more cost effective)
173
CRISPR-CAS
-can be used to design diagnostics and vaccines
-can help cure and prevent disease
-enhances human performance and appearance
-epigenetic modification
-designing new organisms that are more efficient
-bioengineerings
-ecological engineering
174
SLC26A4
-can lead to pendred, DFNB4 and NSEVA
-localizes to the apical membrane of the cells in the spiral prominence and outer sulcus cells in the cochlea
-transitional cells in the cristae ampullaris, utriculi and sacculi
-HL is progressive, fluctuating and late onset
-important for endocochlear potential and endolymphatic sac, made from epithelial cells
-if the product is not produced at the proper time, this results in EVA but EVA is not dependent on this gene
-if only one copy of this gene is present, moderate HL with nonsyndromic findings
-if 2 copies are present, profound SNHL with EVA bilaterally is typical
175
OTOF
-ANSD or profound hearing loss
-correlates with ribbon synapses
-might be because temperature sensitive allele in humans "deafening fever"
-present cochlear microphonic
some variants are moderate to severe/profound
-if no cause for ANSD, genetic testing recommended
176
Pejvakin (PJVK)
-AR
-ANSD
-spiral ganglion neurons
-pre/post lingual mild to profound HL
-truncating mutations can lead to profound SNHL
177
GJB2S
-subtype of GJB2, nonsyndromic HL
178
GJB6
-can be nonsyndromic or syndromic
-can be knocked out- if the GJB2 promoter is not knocked out then hearing will be normal for GJB6
-if GJB2 is touched in GJB6 then hearing will be affected
179
STRC
-mild to moderate HL but might be something that escapes NBHS detection
-nonsyndromic
-not a lot of vestibular issues to it
-there is some evidence that it might be progressive but it is not a very big sample
180
MYO7A
-may cause DFNB11, DFNB2 and Usher 1
-pathophysiology- effects myosin, the sterocilia in the hair cells and the retinal pigmented cells
-HL is similar to STR (mild to moderate)
-onset- progressive (AD) or stable (AR)
-can have vestibular issues sometimes
-there are 559 pathogenic mutations
181
MYO15A
-deafness gene is DFNB3
-pathophysiology- myosin 15, interacts with the tips of the stereocilia (alongation)
-HL is severe to profound, corner audiogram
182
GJB1 (Charcot Marie Tooth)
-if involved with GJB1m would lead to demyelination of the peripheral nerves
-typical symptoms are muscle weakness, atrophy and sensory loss
183
CDH23
-nonsense, frameshift, splice site and missense
-could be a cause of Usher 1 (traditional type, severe to profound SNHL at birth or within year 1)
-vestibular areflexia- clumsy, cannot tell up from down (swimming underwater danger)
-nightblindness/retinitis pigmentosa (narrow visual field) in late childhood to legal blind by 30
184
TMC1
-prelingual moderately severe to profound SNHL
-stereocilia problem
-common cause of deafness in consanguineous Indian Pakistani Turkish and Tunisian families
-can be progressive
185
TMPRS33
-progressive bilateral with variable onset and progression
-sloping audio eventually becoming flat
-varies from mild to profound HL
186
CHD7
-50% of CHARGE syndrome cases have this gene
187
How is the order of the name of the gene important?
-will help to locate it
-order is chromosome number, arm designation then band number
188
Viruses
-much of what we know and what we can do with genome comes from the structure and function of viral and bacterial genomes
-identified by sequence
-responsible for most diseases
-not killed by antibiotics
-has a high rate or mutation
189
GJB2
-AR
-homozygous and biallelic frequent
-depends on the prevalence but this gene may account for 30-40% of AR nonsyndromic HL
-typical congenital onset
-HL is typically moderate to profound SNHL, can be progressive but that is less common, can be mild
-usually symmetric but not always
-very small gene
-more than 130 variants/mutations
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Incidence and kinds of congenital HL
-1/500 prelingual deaf children
-25% of deaf children are idiopathic
-25% are not genetic
-50% are genetic
-of those genetic, 70% are nonsyndromic
of the nonsyndromic cases, 75% are AR, 15-24% are AD, 1-2% are X-linked
-of those that are AR, 50% are from DFNB1
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Hybridization test
-basis of many tests
-the longer and more perfect the match the stronger
-very difficult to use long pieces
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Quantitative fluorescence PCR
-amplifies microsatellite markers (specific to that allele) on chromosomes suspected to be trisomic
-can be done prenatally
-very specific
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Microarray
do not need live cells to do this and can show small changes
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Pedigree- how would it show AD, AR, X-linked, mitochondrial, de novo, somatic
-AD will see it every generation or close to it will be very present
-AR may skip a generation who will then be carriers
-X-linked will see many males being affected compared to females
-Mitochondrial- mom will pass on their mitochondrial on
-de novo- will see nothing then it will pop up
-somatic- not passed on
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Will a base substitution of thymine for guanine or a deletion of guanine have. a larger effect?
Deletion- think about frameshift, it may translate the DNA to a incorrect code leading to bad outcomes
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List 3 genes which are typically related to congenital symmetric severe to profound SNHL
-GBJ2
-Usher
-Pendred
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Will methylation of DNA affect DNA transcription?
Yes
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Whole exome sequencing
sequences the exons of a persons DNA to identify genetic variants that may cause disease
