Inherited Molecular Disease Flashcards by Tatiana Perez

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

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provides gene reference sequences.

National Center for Biotechnology Information

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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

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there is a missing nucleotide. In the example, the C
was deleted or missing

Gene deletion

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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

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you can see a multiple copy of a nucleotide

Copy number variant

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segment of DNA more than 50 kb in size. It copies/duplicates
much longer compared to segmental duplication

Large scale copy number variant

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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

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3 main categories of single gene disorder

→ Autosomal dominant
→ Autosomal recessive
→ X-linked

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single gene disorder follows what law?

mendelian inheritance pattern

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we have one affected parent. 50% chances to be
inherit by the offspring

X-linked dominant

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either one parent is a carrier. produces carrier
offspring and has a very little chance to produce affected offspring

X-linked recessive

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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

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a protein called ??? that is
involved in converting cartilage to bone

fibroblast growth factor receptor 3

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Explain the mutation of Achondroplasia

guanine at 380 codons is substituted by either adenine or cytosine at cDNA position1138

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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

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Where does mutation happen in Alpha-1-antitrypsin deficiency

chromosome 14

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Lab diagnosis for Alpha-1-antitrypsin deficiency

real time PCR and direct sequencing

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is a protein that protects your lungs and is
secreted or produced by your live

Alpha-1 antitrypsin

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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

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tyoe of PKD which mutation is on chromosome 16 (associated in approx..85% of individuals with PKD)

PKD1

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tyoe of PKD which mutation is on chromosome 4 (about 15% of individuals)

PKD2

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is the most common method to diagnose
patients with autosomal polycystic kidney disease.

Genetic linkage analysis

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Deletion of three nucleotides in exon 10 the CFTR gene that leads to
loss of the amino acid phenylalanine at codon 508

Cystic fibrosis

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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.

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

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.

Inherited Molecular Disease Flashcards

(105 cards)