Inherited Molecular Disease Flashcards
It is a starting genomics and a digital nucleic acid sequence
database. It can be a gene of one species or a combination of different
organisms.
Gene reference sequence
provides gene reference sequences.
National Center for Biotechnology Information
It has a single base substitution at an individual site of DNA
sequence. Here we can see that your C was replaced by T
(substitution).
Single nucleotide polymorphism
there is a missing nucleotide. In the example, the C
was deleted or missing
Gene deletion
Inverted gene sequence
it is the rearrangement causing a segment of DNA to be in reverse
orientation. and has improper
positioning/arrangement of the gene sequence
you can see a multiple copy of a nucleotide
Copy number variant
segment of DNA more than 50 kb in size. It copies/duplicates
much longer compared to segmental duplication
Large scale copy number variant
segment of DNA is 1 kb in size usually occurs in 2 or more copies
per haploid genome. Segment of DNA is 1 kb and can be copied
at least 1 or more.
Segmental duplication
3 main categories of single gene disorder
→ Autosomal dominant
→ Autosomal recessive
→ X-linked
single gene disorder follows what law?
mendelian inheritance pattern
we have one affected parent. 50% chances to be
inherit by the offspring
X-linked dominant
either one parent is a carrier. produces carrier
offspring and has a very little chance to produce affected offspring
X-linked recessive
Most frequently encountered type of genetic dwarfism
Characterized by a disproportionately short stature and other skeletal
abnormalities resulting from a defective gene encoding for fibroblast
growth factor receptor 3 (FGFR3)
Achondroplasia
a protein called ??? that is
involved in converting cartilage to bone
fibroblast growth factor receptor 3
Explain the mutation of Achondroplasia
guanine at 380 codons is substituted by either adenine or cytosine at cDNA position1138
An inherited condition that causes low levels of, or no, alpha-1 antitrypsin
(AAT) in the blood , Autosomal codominantly inherited disease that predominantly affects the
lungs and liver
Alpha-1-antitrypsin deficiency
Where does mutation happen in Alpha-1-antitrypsin deficiency
chromosome 14
Lab diagnosis for Alpha-1-antitrypsin deficiency
real time PCR and direct sequencing
is a protein that protects your lungs and is
secreted or produced by your live
Alpha-1 antitrypsin
Is one of the most common forms of polycystic kidney disease
* Is a genetic disorder characterized by the growth of numerous fluid-filled
cysts in both kidneys
* Autosomal dominant
autosomal Polycystic Kidney Disease
tyoe of PKD which mutation is on chromosome 16 (associated in approx..85% of individuals with PKD)
PKD1
tyoe of PKD which mutation is on chromosome 4 (about 15% of individuals)
PKD2
is the most common method to diagnose
patients with autosomal polycystic kidney disease.
Genetic linkage analysis
Deletion of three nucleotides in exon 10 the CFTR gene that leads to
loss of the amino acid phenylalanine at codon 508
Cystic fibrosis
used to detect or know who has cystic
fibrosis (according to the book, it is commonly used to screen for cystic
fibrosis).
Allele-specific hybridization
The healthy individuals are ??? for the wild-type allele and
??? for the CFTR alleles, whereas those affected by the
disease carry two mutant alleles
homozygous; heterozygous
Hybridization is detected by measuring fluorescence emitted by the
? attached to the probe.
fluorophore
Result of CFTR
leads to microbial pathogen colonization in the lungs,
A congenital anomaly of the sixth cranial nerve nuclei with aberrant
innervation supplied from the third cranial nerve.
Duane’s Retraction Syndrome
Duane’s Retraction Syndrome is An autosomal dominant trait in which unique heterozygous missense
mutations are found in the
CHN1 gene.
Duane’s Retraction Syndrome is tested by ?
Direct Sequencing
most effective way
for detection of DMD
Multiplex Ligation-Dependent Probe Amplification
Individuals who have ? have progressive loss of muscle function
and weakness, which begins in the lower limbs
Duchenne Muscular Dystrophy
is the largest gene in the human genome, spanning
2.4Mb and containing 79 exons
Dystrophin
size of Dystrophin protein
427 kDa dystrophin protein
Is the most common monogenic cause of intellectual disability and
autism
X chromosome-linked recessive trait
Fragile X-syndrome
Normally we have ? expansions of the CGGs, but in Fragile X
syndrome, there is 200 or more repeated expansions of CGGs.
40
mutation in Fragile X
syndrome
mutations in the fragile X mental
retardation 1 (FMR1) gene
there is 200 or more repeated expansions of CGGs. arginine
The gold standard fragile X test is ? which
allows concurrent detection of large CGG-repeat expansions and
determination of its methylation status.
Southern blot analysis
Alternatively, ? approaches can be used to characterize
CGG-repeat size and/or AGG-interruption patterns
PCR
A bleeding disorder that slows down the blood cclotting process
* X-linked recessive disorder
Hemophilia
FVIII gene mutation
hemophilia A
FIX gene mutation
hemophilia B
Autosomal dominant genetic
* A progressive neurodegenerative disorder that presents with motor
symptoms, cognitive impairment, and psychiatric disturbances
* Caused by the abnormal expansion of CAG repeats in the HTT gene
Huntington’s Disease
n HD gene, the glutamine chain has abnormal huntington with more than
? glutamine residues
36
Between ? glutamine residues, incomplete penetrance allele can be diagnosed with HD,
might or may not develop HD, or increased risk for HD
36-39 glutamine residues
? complete penetrance of the allele is diagnosed with HD, will
develop HD, and has increased risk for HD
40 or more glutamine residues
Method of choice for Huntington’s disease is ? , but it should be run together with PCR
TP-PCR or triplet repeat
Primed PCR
This gene is coded to produce Fibrillin-1 which is needed for making
microfilaments that help with structure
FBN1 gene
Most common symptom of Marfan Syndrome is
myopia
Individuals with Marfan Syndrome has increased risk of having
glaucoma
and early cataract formation
What is used to identify Marfan Syndrome
Single-Strand Conformation
Polymorphism (SSCP),
Denaturating High Performance Liquid
Chromatography, and
Direct sequencing
One of the most common inherited disorders of connective tissue
Marfan Syndrome
Caused by a mutation in the hemoglobin-β gene found on
chromosome 11
Sickle Cell Disease
mutation in sickle cell disease
there is a mutation
or replacement to valine in chromosome 11 which leads to sickle cell
disease
lab test for sickle cell disease
Sickle Solubility testing, Hemoglobin Electrophoresis, HPLC, and IEF
Autosomal recessive inherited diseases of the blood that affect a
person’s ability to produce hemoglobin, resulting in anemia
thalassemia
characterized by reduced or absence of αglobin chain synthesis and is caused mainly by deletions in the αglobin gene complex located on Chromosome 16
Alpha-thalassemia
characterized by reduced or absence of βglobin chains located on Chromosome 11
Beta-thalassemia
These disorder can be detected through PCR and High-Resolution melting analysis
Treatment of thalassemia is usually
blood transfusion
A fatal autosomal recessive genetic disorder, most commonly occurring
in children
* Caused by mutations in the HEXA (hexosaminidase-A) gene localized
on chromosome 15
Tay-Sachs Disease
Three different forms of Tay-Sachs Disease
classic infantile, juvenile, and adult late-onset
differentiate classic infantile and juvenile form of Tay-Sachs Disease
Classic infantile
→ The most common causes macular cherry red spots, blindness,
intractable seizures, and paralysis
Juveniles and Adult forms
→ Are very rare with a later onset and slower course
▪ Juvenile or subacute GM2 gangliosidosis is characterized by gait
disturbances, incoordination, speech problems, and intellectual
impairment
Can be used to detect common mutations by using normal and mutant
primers as reverse primers and common forward primers
used for Tay-Sachs Disease
Amplification Refractory Mutation System-Polymerase Chain Reaction
Genetic disorders are ? when they are associates with the
effects of many genes.
polygenic
Such disorders also can be ? because they do not follow
simple Mendelian pattern of inheritance and can be influenced by
several different lifestyle and environmental factors
multifactorial
true or false
An individual’s genetic background usually is sufficient to cause the
disorder in most polygenic disorders and render an individual more
susceptible to the disorder
false, should be not sufficient
Currently used to map polygenic disease
– GENOME WIDE ASSOCIATION
principle of – GENOME WIDE ASSOCIATION
Genotyping of hundreds of thousands of genetic variants and
comparison of allele distributions between cases with a disease and
controls without the disease.
Give the POLYGENIC DISORDERS
Alcohol Dependence
* Charcot-Marie-Tooth Disease
* Cri du chat Syndrome
* Cardiovascular Disease
Alcohol metabolizing enzyme genes:
ALDH2:
ADH1B:
Alcohol metabolizing enzyme genes: East Asian populations
ALDH2
Alcohol metabolizing enzyme genes: European-American
ADH1B
Alcohol metabolizing enzyme genes: African- American
populations
ADH1B
most common inherited neuromuscular disorder
* symptoms include slowly progressive distal muscle weakness,
muscle atrophy, and sensory loss of the lower and then upper limbs
CHARCOT-MARIE-TOOTH DISEASE
it is also called hereditary sensory and motor neuropathy
CHARCOT-MARIE-TOOTH DISEASE
CHARCOT-MARIE-TOOTH DISEASE two main groups:
→ Demyelinating type (CMT1)
→ Axonal type (CMT2)
differentitate CMT1 AND CMT2
→ Demyelinating type (CMT1) - loss of myelin on peripheral neurons
→ Axonal type (CMT2) - loss of peripheral neurons
CMT1 – most common gene
PMP22
CMTX – most common gene
GJB1
The majority of patients with CMT have ?
inheritance, although many will have forms with X-linked (CMTX) or
autosomal recessive (AR) (CMT4) inheritance.
autosomal dominant
The three next most common genetic forms of CMT are those caused
by ? ? ?
GJB1, MPZ, and MFN2.
also known as 5p-syndrome and cat cry syndrome
Cri Du Chat Syndrome
Cri Du Chat Syndrome Hallmark features:
o high-pitched monotonous cry –reason for “cat cry”
syndrome
o low birth weight
o microcephaly
o hypotonia – weak muscles
o poor growth
o developmental delay
Cri Du Chat Syndrom is Diagnosed by a combination of
microarray and FISH analyses
a rare genetic condition caused by the deletion of genetic material on
the small arm (the p arm) of chromosome 5
Cri Du Chat Syndrom
GWAS used to examined cardiovascular aging markers: 42 genetic loci
identified
o 16: associated with known risk factors
o 10: associated with increased LDL
o 5: with increased BP
o 4: with increased TAG
o 7: with decreased HDL
It is a leading cause of morbidity and mortality in developed
countries, has a significant genetic background.
cardiovascular disease
By the dysfunction of the mitochondria, it will lead/characterized by
? production leading to
oxidative stress
increased ROS (Reactive Oxygen Species)
Problem with ATP in kidnet causes
– Fanconi’s syndrome
Problem with ATP in Blood causes
– Pearson’s syndrome
Problem with ATP in Pancreas causes
– diabetes mellitus
Problem with ATP in liver causes
– hepatopathy
Problem with ATP in eye causes
optic neuropathy
Problem with ATP in heart causes
cardiomyopathy
most common hereditary optic neuropathy that severely impairs
vision
DOMINANT OPTIC ATROPHY
caused by a loss of retinal ganglion cells located only in the inner retina
and projecting their axons via the optic nerve to the brain
DOMINANT OPTIC ATROPHY
is multifunctional protein located within the mitochondrial inner
membrane, which regulates a number of critical cellular functions
OPA1
caused by autosomal recessive mutations in mitophagy related
proteins, such as PINK1 and Parkin
Parkinson’s Disease
accumulation of ? resulting in an excessive
mitochondrial fission, oxidative stress and reduced ATP production
Drp1
True or false
Mutations in α-synuclein (SNCA) and leucine-rich repeat kinase2
(LRRK2) genes are responsible for late-onset disease of parkinson
True or false
True or false
Parkin (PARK2), ubiquitin carboxy-terminal hydrolase L1 (UCHL1), PTEN Induced Putative Kinase1 (PINK1), oncogene DJ1 (DJ1)
are responsible for early onset.
True
usually an isoprocess of selective removal of damage or
unnecessary mitochondria. (
Mitophagy
Parkinson’s disease can be diagnosed by
PCR, MLPA or NextGeneration Sequencing.
