Genetics Main Flashcards
1
Q
Genes for connexin deafeness
A
GJB
2
Q
Gene GJB2 =
A
Connexin 26; protein
3
Q
Where is connexin found?
A
Connexins are found in non sensory epithelial & supporting cells
4
Q
what is Connexin?
A
- Inherited non syndromic HL (mild to serve) and deafness.
- Mostly recessive but can be dominate, very rare X-linked
Connexins are found in non sensory epithelial & supporting cells
5
Q
True or false
30% or more of autosomal recessive nonsyndromic hearing loss is caused by Connexin 26 (GJB2 gene) mutations
A
FALSE
50% or more of autosomal recessive nonsyndromic SNHL hearing loss is caused by Connexin 26 (GJB2 gene) mutations
6
Q
Cx26 is thee causative gene in what locus
A
DFNB1- MOST COMMON (AR)
DFNA3- AD
7
Q
Does connexin follow, independant assortment , Mandelain law?
A
no, GJB2 &GJB6 influence one another
Genes GJB2 & GJB6 Code for proteins connexin 26 and connexin 30 and are closely linked on chromosome 13. Closeness = mutation on GJB6 can influence the expression of GJB2.
Meaning You can have hearing loss w/ 2 gene mutations on GJB2 or 2 gene mutations on GJB6 or 1 on 6 & 1 on 2
8
Q
Nonsyndromic loci
DFN
A
Nonsyndromic loci
DFN= Deafness neurosensory
A= Autosomal recessive
B= Autosomal Domiante
X= X-linked recessive
Y= Y-linked
M=Modifer
AUNA= Auditory Nuropathy
OTSC= Otosclerosis
9
Q
Loci identification
A=
A
A= Autosomal Dominate
10
Q
Loci identification
B=
A
B= Autosomal Recessive
11
Q
Loci identification
X=
A
X-linked recessive
12
Q
Loci identification
Y=
A
Y-linked
13
Q
Loci identification
M=
A
M=Modifer
14
Q
Loci identification
AUNA=
A
AUNA= Auditory Nuropathy
15
Q
Loci identification
OTSC=
A
OTSC= Otosclerosis
16
Q
what is
DFNA=
A
DFNA= Autosomal Domiante
17
Q
DFNB=
A
DFNB= Autosomal Recessive
18
Q
DFNX=
A
DFNX= X-Linked recessive
19
Q
DFNY=
A
DFNY= Y-linked
20
Q
DFNM=
A
DFNM=Modifer
21
Q
AUNA=
A
AUNA= Auditory Nuropathy
22
Q
OTSC=
A
OTSC= Otosclerosis
23
Q
Connexin 26
- Gene
- Cauative Gene
- Inheritance
- Common Mutation
- Found in
- audio
A
- GJB2 Gene mutation
- DFNB1 or DNFA3
- Recessive (MC) or Dominate
- Del35G- Common in Caucasians
- found throughout body
really know= Inner ear, Supporting cells and non-sensory epithelial - Congenital, Bilateral, Mild to profound. (rare unilateral)
24
Q
Connexin 30
- Gene
- causative gene
- Inheritance
A
- GJB6
- DFNA3
- Dominate
25
Connexin 32
- Gene
- Inheritance
- Example
- DFNX
- X-Linked
- Charcot-Marie-tooth disease
26
True or False
A multitude of syndromes that include abnormalities of ear and facial defects come from the first and thrid brachial arches?
FALSE
A multitude of syndromes that include abnormalities of ear and facial defects come from the first and second brachial arches
27
How many branchial arches
- initally
- later
- 1-6 branchial arches
- 4 branchial arches
- 5 disappears
- 4 & 6 fuse together
28
What develops from 1st & 2nd Branchial arches?
Outer ear, Middle ear & face
29
what forms the External & Middle ear? (short)
1st & 2nd arche, Their pouches, cleft & neural crest cells form the external and middle ear
30
What does the mesoderm from the 1st & 2nd B Arches form?
Facial and auditory muscles
31
Every each has its own what?
Nerve, Cartilage & Artery
32
2nd,3rd and 4th cleft form the cervical sinus that will later disappear. If the cervical sinus does not disappear this forms what?
forms the lateral or bronchial cysts or fistula.
33
External Canal is formed from
External Canal formed from 1st & 2nd Cleft
begins @ wk 6 1st left tunnels & develops until wk 26 w/meatal plug opening
34
External Canal formation steps
External Canal formed from 1st & 2nd Cleft
begins @ wk 6 1st left tunnels & develops until wk 26 w/meatal plug opening
35
The external Ear matures until what age?
7 years
36
what forms the TM layers (3)
Outer= ectoderm ; meatal plug
middle layer= mesoderm, from neural crest cells
inner layer = ectoderm
37
Tympanic membrane formation
& three layers
at border of meatal plug
outter- endodermal meatal plug
middle- mesoderm; neural crest cells
outer- ectoderm
38
Branchial Arch 1 develops what
- Nerve
- Muscle
- Skeletal Structure
*SUSPECTED QUESTION *
1st arch
- Trigeminal Nerve - CN 5
- Tensor Tympani & Tensor Palatini
- Malleus & incus
39
Branchial Arch 2 develops what
- Nerve
- Muscle
- Skeletal structure
2nd arch
- Facial nerve - CN 7
- Stapedius Muscle
- Stapes
40
Tympanic Cavity & ET development
formed from 1st pouch & ectoderm
TC- Distal 1st pouhc
ET- proximal 1st pouch
41
Ossicle formation
1st & 2nd arches
made of cartilage
TC surround month 8
42
1st & 2nd Branchial Arch syndromes
*SUSPECTED QUESTION *
Treacher Collins
Pierre Robins
Sticklers
43
The Labyrinth will develop into
cochlea & Vestibular sytem
44
Inner ear development
begins at 22 days
otic placode Thickens & endodermal Part invaginates to form otic pit
otic pit = Otic Vesicle
OV splits into ventral and doral
Ventral = Saccule & Cochlear duct
Dorsal = SSC, Utricle and endolympathic duct
45
Cochlea development
Otic placode invaginates = otic pit
otic pit = Otic vesicle
OV split into ventral and dorsal
Ventral= cochlear duct & saccule
dorsal = SSC, Utricle & endolympatic duct
@wk 6 saccule pole = cochlear duct
cochlear duct extends penetrating connetive tissue in a spiral
@ week 8 - 2 3/4 spiral is complete = cochlea
46
Vestibular system
Otic placode invaginates = otic pit
otic pit = Otic vesicle
OV split into ventral and dorsal
Ventral= cochlear duct & saccule
dorsal = SSC, Utricle & endolympatic duct
@ week 6 flattened pockets, central potrion dissapers to flattened pockets
giving rise to SSC
SSC, uticle & saccule filled with endolymph
bone forms around SSC
47
1st & 2nd brachial Arch syndrome Symptoms
Cleft lip/ cleft palate
small lower jaw
external auditory canal abnormalities or atresia
48
Mitosis cycle
Somatic Cells
Interphase- G1,S &G2
Mitosis- PMAT
- Prophase
- Metaphase
- Anaphase
-Telophase
Cytokinesis- division of cytoplasm , development of 2 identical diploid daughter cells.
49
Mitosis key points
*****
Somatic Cell, 2 identical diploid daughter cells, 1 division cycle, replaces dead cells
49
Meiosis
Germ cells
Meiosis 1 = PMAT & Cyokinesis.
- ends with 46 chromatid, 23 pairs
Meiosis 2= PMAT& C
- ends with 4 haploid daughter cells
50
Meiosis Key Points
Germ cells, 2 division cycles, ends with 4 haploid daughter cells, produces gametes,
51
Humans have______ chromosome
Humans have 23 chromosome pairs, 46 chromatids
52
nucleotides and base pairing
DNA
Adenine & Guanine
Cytosine & Thymine
*remember AG, Alyssa garza*
53
nucleotides and base pairing
RNA
Adenine & Guanine
Cytosine & Uracil
*remember AG, Alyssa garza*
54
what are the three types of point mutations?
nonsense, silent mutations and missense mutation
55
what are nonsense mutations?
codes for a stop codon, prematurely stopping a protein translation. all nonsense mutations are bad.
56
what are silent mutations?
is when it codes for the same amino acid but with the wrong or incorrect codon. but the result is the same.
EX: UUU or UUC they both = phenylalanine
57
what are missense mutation?
two types of missense mutations. Conservative and non-conservative
58
what is Conservative missense mutation?
results in a different amino acid but they are not problematic. as long as you get a result that is similar to the original amino acid.
59
what is non- Conservative missense mutation?
Not a forgiving mutation, has a phenotypic effect. it could be lethal if it is an amino acid that do go together or it could juts result in an amino acid that the protein didn't need.
60
frame shift mutation
can occur because of insertion or deletions of a single or more base pair.
it codes incorrectly since it only read 3 at a time.
original: ACG AGG ACU GCA
deletion example A CGA GGA CUG CA
insertion example : AAA CGA CGA GGA CUG CA
61
genetic testing; benefits
● accurate diagnosis and prognosis
● Provide scientific explanations of why the problem occurred, and therefore, preventing/removing the blame game
● Recognition of the risk of associated structural anomalies (e.g., congenital heart defects, JLNS)
● Recognition of the risk of associated developmental handicaps (e.g., learning & intellectual disability)
● Provide accurate recurrence risk for offsprings
62
genetic testing; potential issues not seen with other medical tests
● Provides information affecting reproductive choices
● Misassigned paternity (dad may not be the biological dad)
● Insurance discrimination
● The Deaf community has a predominantly negative attitude towards genetics and genetic testing
63
Chromosomal abnormalities (number, structure)
Monosomy: deletion of a chromosome (missing 1 chromosome) Often lethal, not survivable to any autosome (somatic cells). Exception sex chromosome can result in live birth.
Trisomy: addition of a chromosome (3 chromosomes total)
MOST COMMON: 21, 18, 13
Nullisomy: no chromosome for that pair - lethal
64
Down syndrome
Trisomy; Chromosome 21
65
Trisomy' s
numbers and disorder
○ 21 Downs
○ 18 Edwards
○ 13 Patau
○ X - Klinefelters
66
Genomic Imprinting
- what its is
- Disorder w/ it
Phenotype changes based on which parent passes down the gene
Prader Willi Syndrome
Deletion of chromosome 15 of paternal origin
Angelman syndrome
Deletion of chromosome 15 of maternal origin
67
Genetic Anticipation
Anticipation: the worsening of symptoms of a genetic disease from one generation to the next
68
Allelic Expansion
Allelic expansion: increase in gene size and caused by an increase in the number of trinucleotide based sequences
Myotonic dystrophy
Huntington's disease
Fragile X Syndrome
69
Mitochondrial Inheritance
- what is it
- example
- Only mother can pass down & 100% of offspring inherit
- Leber’s hereditary optic neuropathy (sudden loss of central vision)
70
Polygenic
One gene → one small impact on phenotype
71
Multifactorial
resulting from the interplay of multiple environmental factors with multiple genes
Oculo-Aricular-Vetebral (OAV)
72
Y-Linked Inheritance
Rare! Passed from father to son (the fathers Y has to be passed down to be the sons Y)
No father to daughter transmission
73
X-linked Dominant Inheritance
-what
- ex
- the female with the abnormal gene on the X chromosome will manifest the disease condition regardless of what is on the other X-chromosome
- BOTH SONS AND DAUGHTERS HAVE A 50% CHANCE OF INHERITING THAT TRAIT FROM THEIR MOTHER AND EXPRESSING
no- father to son
- alports
74
X-linked Recessive Inheritance:
- No father to son transmission
Transmission from unaffected female carriers to males
- All daughters of a male with the trait will be carriers (supporting X)
Carrier females will have a
50% chance to have sons with abnormal trait
50% to have carrier daughters
50% to have normal offsprings
ex: Color blindess, Hemophillia
75
Autosomal Recessive Inheritance:
Two identical copies of the gene are required
25% chance of occurrence per pregnancy
- Pendred, ANSD,Ushers
76
Treacher Collins syndrome
- Inheratance
- From
- HL
- Symptoms
-DD
Treacher Collins syndrome
Autosomal Dominate
1st Arch Syndrome
Bilateral CHL
Peanut ear/atreria
Smaller lower jaw
Large mouth
Coloboma- eye
DD: OAV
77
BOR: Branchio-oto-renal
- Inheratance
- From
- HL
- Symptoms
-DD
- Autosomal Dominate
- 2nd arch
- Conductive,SNHL, Mixed
- EARS & KIDNEYS
-Renal/kidney Problems
- Pinna Malformation
- HL
-DD: Alports Syndrome
78
OAV; Oculo-Aurticulo-vertebral
- Inheratance
- HL
- Symptoms
-DD
- Multifactoral
- CHL-COMMON
-SNHL-rare
- EYE,EAR,VETEBRA
Small lower jaw
Spina Bifida,scoliosis
Unilateral or bilateral
Deafness
Blindness
79
CHARGE
- symptoms
- Inheritance
CHARGE
C- Coloboma of the eye
H- Heart Defects
A- Atresia of nasal
R- Retard- development
G- Gential abnormalities
E- Ear Abnormlies and or deafness
SNHL, Progressive
- Kidney problems
-behavioral issues
-autosomal dominate
80
Ushers, all types
Progressive SNHL
Blindness w/Redness Pigmentosa
Autosomal Recessive
Type 1
Congenital Severe - profound SNHL
Abnormal Vestib - gait ataxia
Delayed motor
Progressive Vision loss (Blindness)
w/Redness Pigmentosa
Type 2
Congenital mild-severe SNHL
Normal Vestibular
Progressive Vision loss (Blindness)
w/Redness Pigmentosa
Type 3
Rare
Progressive SNHL
Progrestive Vestibular dysfunction
Progressive Vision loss (Blindness)
w/Redness Pigmentosa
DD: OAV????
81
Ushers type1
Type 1
Congenital Severe - profound SNHL
Abnormal Vestib - gait ataxia
Delayed motor
Progressive Vision loss (Blindness)
w/Redness Pigmentosa
82
Ushers type 2
Type 2
Congenital mild-severe SNHL
Normal Vestibular
Progressive Vision loss (Blindness)
w/Redness Pigmentosa
83
Ushers type 3
Type 3
Rare
Progressive SNHL
Progrestive Vestibular dysfunction
Progressive Vision loss (Blindness)
w/Redness Pigmentosa
84
Norrie Syndrome
- Inheratance
- HL
- Symptoms
-DD
Norrie Syndrome
- X-Linked
- Progressive SNHL
- Progressive Blindness
- Seixures
- mental issues (bipolar etc)
-DD: CMV, Usher, Rubella
85
Crouzon’s syndrome
-AD
- CHL
- buldging eyes, small lower jaw, vision problems
86
Sticklers
- Inheratance
- HL
- Symptoms
-DD
Sticklers
-Autosomal Dominant
-Underdeveloped middle of face
-Small lower jaw
-Near-sightedness
-CHL or Mixed
-Joint problems
87
Achondroplasia
- symptoms
-inheritance
Dwarfisum
Autosomal Dominate
Short extreamties (Arms & legs)
Normal Abdominal
88
Osteogenesis imperfecta
- symptoms
- inheratnce
Osteogenesis imperfecta
Autosomal Dominant
Cardiovasular problems
Blue Sclara
CHL or mixed
89
Alport syndrome
Inhertance
symptoms
DD
- X-Linked Dominant or X-Linked Recessive
-AR or AD- VERY RARE
-SNHL
-Nephritis
dd: BOR
90
Charcot Marie tooth disease
- Symptoms
- inheritance
Charcot Marie tooth disease
SNHL, slow progressive
absent reflexes (limb)
- X- Linked recessive
- AD
- AR
91
Frederick's ataxia
- Symptoms
- inheritance
Frederick's ataxia
Autosomal Recessive
Nystagmus
speech dysarthria
absent Babinski
Scoliosis
enlarged heart
SNHL
92
Neurofibromatosis (NF) 1
AUTOSOMAL DOMINATE
More than 6 Cafe Au Lait spots
Cutaneous and subcutaneous tumors ( on or under skin)
increased number
93
NF 2
autosomal dominant & spontaneous mutation 50/50 %
0 - 6 Cafe Olé spots
Progressive vision loss
bilateral acoustic neuroma
Less common than NF1
94
JLNS,
-inheratnce
-symptoms
-HL
-DD
**
JLNS,
Autosomal Recessive
Bilateral SNHL
heart issues, heart disease
sudden death
DD; Ward-Roman Syndrome
95
pendreds
-Inheratnce
- Symptoms
- HL
-DD
- Autosomal Recessive (2nd MC)
- Thyroid issue
- EAV Enlarged vestibular aqueduct
- Goiter
- SNHL 100%
dd: SNHL non-syndromic
connexin deafness
96
Waardenburg’s
- inheratnce
- Name how many types
autosomal dominant
Most common autosomal dominant
four types (WS 1- WS4)
97
Waardenburg’s 1
Most common out of all 4 types
autosomal dominant
Most common autosomal dominant
wardenburg syndrome1
- bilateral or unilateral Hearing loss
- white for Forelock
- albinism
98
wardenburg syndrome2
white for Forelock
Albinism
unilateral Hearing loss - less likely
99
wardenburg syndrome3
White forelock of hair
abnormal shortness of Limbs
No HL
100
wardenburg syndrome4
rare
White for lock of hair
Deafness
101
Sugar + Base + Phosphate = NUCLEOTIDE
Base Pairing: A+T, C+G (consonants)
3 STOP CODONS: UAA, UAG,UGA
1 START CODON: AUG (methionine)
