Hereditary Disorders + Molecular Diagnosis of Genetic Disorders (P) Flashcards

Question

What is the purpose of SNPs?

Answer 1

They represent variation at single nucleotide positions

Answer 2

These are form of genetic variation consisting of diff #s of large contiguous stretches of DNA

Answer 3

Gene-coding sequences

Answer 4

CNVs may underlie a large portion of human phenotypic diversity

Answer 5

1) Disease-causing mutations 2) Susceptibility variants 3) Disease modifiers 4) Determinants of response to therapy 5) Neutral variants

Answer 6

It is defined as heritable changes in gene expression that are not caused by alterations in DNA sequence

Answer 7

It concerns itself w/ the measurement of all proteins expressed in a cell or tissue

Answer 8

It is computer-based techniques that can manage vast collections of data

Answer 9

*Modulate the translation of target mRNAs into their corresponding proteins

Answer 10

Andrew Fire and Craig Mello

Answer 11

Nobel prize in Physiology and Medicine

Answer 12

Code for microRNA

Answer 13

It is 21 - 30 nucleotides long

Answer 14

It do not code for protein but it inhibits gene expression

Answer 15

These are derived from one's parents and are transmitted in the germ line through the generations therefore are familial

Answer 16

It simply implies "born with"

Answer 17

670 per 1,000

Answer 18

Demonstrable chromosomal abnormality

Answer 19

These are defined as a permanent change in the DNA

Answer 20

1) In germ cells, these are transmitted to the progeny 2) In somatic cells, these do not cause hereditary diseases but are important in the genetics of cancers and some congenital malformations

Answer 21

Inherited diseases

Answer 22

In partial or complete deletion of a gene or, more often, affect a single base

Answer 23

1) Point mutations within coding sequences 2) Mutations within noncoding sequences 3) Deletions and insertions 4) Trinucleotide-repeat mutations

Answer 24

1) Missense mutations | 2) Nonsense mutations

Answer 25

1) Concervative missense mutations | 2) Nonconcervative missense mutations

Answer 26

Occurrence of frameshift mutations

Answer 27

These mutations are characterized by amplification of a sequence of 3 nucleotides

Answer 28

1) Disorders related to mutations in single gene w/ large effects 2) Chromosomal disorders 3) Complex multigenic disorders (polymorphisms)

Answer 29

Highly penetrant

Answer 30

Single gene mutations

Answer 31

The classic Mendelian pattern of inheritance = Mendelian disorders

Answer 32

1) Autosomal dominant 2) Autosomal recessive 3) X-linked disorders

Answer 33

1) Huntington disease 2) Neurofibromatosis 3) Myotonic dystrophy 4) Tuberous sclerosis

Answer 34

Polycystic kidney disease

Answer 35

Familial polyposis coli

Answer 36

1) Hereditary spherocytosis | 2) von Willebrand disease

Answer 37

1) Marfan syndrome 2) Ehlers-Danlos syndrome (some variants) 3) Osteogenesis imperfecta 4) Achondroplasia

Answer 38

1) Familial hypercholesterolemia | 2) Acute intermittent porphyria

Answer 39

1) Cystic fibrosis 2) Phenylketonuria 3) Galactosemia 4) Homocystinuria 5) Lysosomal storage diseases 6) Alpha(sign)1-Antitrypsin deficiency 7) Wilson disease 8) Hemochromatosis 9) Glycogen storage diseases

Answer 40

1) Sickle cell anemia | 2) Thalassemias

Answer 41

Congenital adrenal hyperplasia

Answer 42

1) Ehlers-Danlos syndrome (some variants) | 2) Alkaptonuria

Answer 43

1) Neurogenic muscular atrophies 2) Friedreich ataxia 3) Spinal muscular atrophy

Answer 44

Duchenne muscular dystrophy

Answer 45

1) Hemophilia A and B 2) Chronic granulomatous disease 3) Glucose-6-phosphate dehydrogenase deficiency

Answer 46

1) Agammaglobulinemia | 2) Wiskott-Aldrich syndrome

Answer 47

1) Diabetes insipidus | 2) Lesch-Nyhan syndrome

Answer 48

Fragile-X syndrome

Answer 49

1) Enzyme defects 2) Defects in membrane receptors 3) Alterations in structure, function, or quantity of non-enzyme proteins 4) Mutations resulting in unusual rxns to drugs

Answer 50

(all *) 1) Phenylalanine hydroxylase 2) Splice-site mutation: reduced amount 3) Phenylketonuria 1) Hexosaminidase 2) Splice-site mutation or frameshift mutation w/ stop codon: reduced amt 3) Tay-Sachs disease 1) Adenosine deaminase 2) Point mutations: abnormal protein w/ reduced act 3) Severe combined immunodeficiency

Answer 51

1) Alpha(sign)1- Antitrypsin 2) Missense mutations: impaired section from liver to serum 3) Emphysema and liver disease

Answer 52

1) Low-density lipoprotein receptor 2) Deletions, point mutations: reduction of synthesis, transport to cell surface, or binding to low-density lipoprotein 3) Familial hypercholesterolemia

Answer 53

1) NA 2) NA 3) NA

Answer 54

1) Hemoglobin 2) Deletions: reduced amt 3) Alpha(sign)-Thalassemia

Answer 55

1) NA 2) Defective mRNA processing: reduced amt 3) Beta(sign)-Thalassemia

Answer 56

1) NA 2) Point mutations: abnormal structure 3) Sickle cell anemia

Answer 57

1) Cystic fibrosis transmembrane conductance regulator 2) Deletions and other mutations: nonfunctional or misfolded proteins 3) Cystic fibrosis

Answer 58

1) NA 2) NA 3) NA

Answer 59

1) Collagen 2) Deletions or point mutations cause reduced amt of normal collagen or normal amts of defective collagen 3) Osteogenesis imperfecta: Ehlers-Danlos syndromes

Answer 60

1) Fibrillin 2) Missense mutations 3) Marfan syndrome

Answer 61

1) Dystrophin 2) Deletion w/ reduced synthesis 3) Duchenne / Becker muscular dystrophy

Answer 62

1) Spectrin, ankyrin, or protein 4.1 2) Heterogenous 3) Hereditary spherocytosis

Answer 63

1) Factor VIII 2) Deletions, insertions, nonsense mutations, and others: reduced synthesis or abnormal factor VIII 3) Hemophilia A

Answer 64

1) Rb protein 2) Deletions 3) Hereditary retinoblastoma

Answer 65

Human somatic cells contain 46 chromosomes, comprise 22 homologous pairs of autosomes and 2 sex chromosomes, XX in the female and XY in the male

Answer 66

It is the study of chromosomes

Answer 67

It is the basic tool of the cytogeneticist

Answer 68

1) Total # of chromosomes 2) Sex chromosome complement 3) Description of abnormality

Answer 69

47, XY, +21

Answer 70

1) Due to an abnormal # of chromosomes | 2) Due to alterations in the structure of 1 or more chromosomes

Answer 71

46, XX or 46, XY

Answer 72

It is the exact multiple of a haploid

Answer 73

It not a multiple of 23

Answer 74

1) Monosomies | 2) Trisomies

Answer 75

1) Deletions 2) Ring chromosome 3) Inversion 4) Isochromosome 5) Translocation

Answer 76

1) Interaction bet variant forms of genes and environmental factors 2) Environmental influences modify the phenotypic expression of complex traits

Answer 77

It is a genetic variant that has at least 2 alleles

Answer 78

These occurs in at least 1% of the population

Answer 79

False, because DNA-based analysis has become a powerful tool for the dx of human disease

Answer 80

1) It is now possible to identify mutations at the DNA lvl and offer diagnostic tests for an increasing # of genetic disorders 2) Molecular tools have become extremely important in discovery of the genetic basis of common complex disorders such as DM, atherosclerosis, and cancer

Answer 81

1) Molecular assays are remarkably sensitive | 2) DNA-based tests are not dependent on a gene product that may be produced only in certain specialized cells

Answer 82

The use of PCR allows several million-fold amplification of DNA or RNA, making it possible to use as few as 1 or 100 cells for analysis. 0.1 uL of blood or cells scraped from buccal mucosa can supply sufficient DNA for PCR amplification

Answer 83

(E.g. brain) or expression of a gene that may occur late in life. Because the defective gene responsible for inherited genetic disorders is present in germ line sxs, every postzygotic cell carries the mutation

Answer 84

1) A mother of advanced age (35 yrs >) because of greater risk of trisomies 2) A parent who is a carrier of a balanced reciprocal translocation, robertsonian translocation, or inversion (in these cases the gametes may be unbalanced, and hence the progeny would be at risk for chromosomal disorders) 3) A parent w/ a previous child w/ a chromosomal abnormality 4) A fetus w/ ultrasound-detected abnormalities 5) A parent who is a carrier of an X-linked genetic disorder (to determine fetal sex) 6) Abnormal lvls of AFP, beta(sign)HCG, and estriol performed as the triple test

Answer 85

1) Multiple congenital anomalies 2) Unexplained mental retardation and/or developmental delay 3) Suspected aneuploidy (e.g. features of Down syndrome) 4) Suspected unbalanced autosome (e.g. Prader-Willi syndrome) 5) Suspected sex chromosomal abnormality (e.g. Turner syndrome) 6) Suspected fragile-X syndrome 7) Infertility (to rule out sex chromosomal abnormality) 8) Multiple spontaneous abortions (to rule out the parents as carriers of balanced translocation; both partners should be evaluated)

Answer 86

1) Dx and management of cancer | 2) Dx and management of infectious disease

Answer 87

1) Detection of tumor-specific acquired mutations and cytogenetic alterations 2) Determination of clonality as an indicator of a neoplastic (e.g. nonreactive) condition 3) Identification of sp genetic alterations that can direct therapeutic choices (e.g. HER2 / Neu in breast cancer or EGFR mutations in lung cancer) 4) Determination of treatment efficacy (e.g. minimal residual disease detection of BCR-ABL1 by PCR in CML) 5) Detection of Gleevec-resistant forms of CML and gastrointestinal stromal tumors

Answer 88

*Cytogenetic alterations

Answer 89

BCR-ABL1 in chronic myeloid leukemia (CML)

Answer 90

1) Detection of microorganism-specific genetic mat for definitive dx (e.g. HIV, mycobacteria, HPV, herpes virus in CNS) 2) Identification of sp genetic alterations in the genomes of microbes that are associated w/ drug resistance 3) Determination of treatment efficacy (e.g. assessment of viral loads in HIV and hepatitis C virus infection)

Answer 91

False, because though DNA replication is conceptually simple, the process is complex and involves a # of accessory proteins and enzymes

Answer 92

1) Extreme heat 2) Hydrogen bond disrupters 3) pH outside 4 - 9

Answer 93

It is the process of unwinding DNA via the use of temp

Answer 94

It is the temp at w/c 50% of dsDNA is converted into single stranded DNA

Answer 95

Adenine-to-thymine (AT) pair vs the cytosine-to-guanine (CG) pair in the DNA strand

Answer 96

The AT pair has a weaker bond compared to the CG pair

Answer 97

Higher melting point

Answer 98

It is an equipment that raises and lowers the temp of the sx in cycles w/c is very important in the process of unwinding the DNA

Answer 99

1) Denaturation 2) Annealing 3) Extension

Answer 100

It is the unwinding of strands through heat

Answer 101

It is the attachment of primer to the target segment through a cooler temp

Answer 102

It is the addition of nucleotides to the primer w/ a warm temp

Answer 103

1) Denaturation: 1 min at 94 DC 2) Annealing: 45 secs at 54 DC - > forward and reverse primers are used 3) Extension: 2 mins at 72 DC - > only deoxynucleotide triphosphates (dNTPs) are used

Answer 104

1) Via the use of restriction enzymes 2) Via the use of fluorescently-labeled nucleotides 3) PCR analysis for short gene segments 4) Via the use of southern blot w/c is used for mutations involving large segments of genetic mat

Answer 105

1) Southern Blotting 2) FISH 3) Array-based Comparative Genomic Hybridization (Array CGH)

Answer 106

It is an inherited RBC disorder

Answer 107

Normal RBCs are round like doughnuts, and they move through small blood tubes in the body to deliver O2. If these normal RBCs become sickle, these become hard, sticky, and shaped like sickles used to cut wheat. When these hard and pointed RCs go through the small blood tube, they clog the flow and break apart. This can cause pain, damage, and a low blood ct, or anemia

Answer 108

It is a common hereditary hemoglobinopathy that occurs primarily in individuals of African descent

Answer 109

It is caused by a point mutation in the 6th codon of beta(sign)-globin that leads to the replacement of a glutamate residue w/ a valine residue

Answer 110

The abnormal physiochemical properties of the resulting sickle hgb (HbS)

Answer 111

1) Chronic hemolysis 2) Microvascular occlusions 3) Tissue damage

Answer 112

1) Irreversible sickled cell 2) Reticulocytosis 3) Target-cells 4) Howel-jolly bodies

Answer 113

1) Bone marrow hyperplasia 2) Bone marrow resorption leads to new bone formation 3) Hyperbilirubinemia / pigmented gallstones formation

Answer 114

Presence of HbS

Answer 115

1) "Crew cut" lesions in X-ray of skull | 2) Prominent cheek bones