Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

M2M Final Exam > Unit II - Genetics > Flashcards

Unit II - Genetics Flashcards

1
Q

Acrocentric Chromosomes

A

Chromosomes whose centromeres are located near the end of the chromosome; stalks and satellites on the short arms contain repetitive DNA sequences that code for rRNA

Chromsomes 13, 14, 15, 21, and 22

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Imprinting

A

Non-coding DNA sequences (imprinting centers) recruit DNA methyltransferase complexes that methylate CpG dinucleotides near the IC on that chromosome; imprinting is established and maintained in one of the two germ lines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Chromosomal Microarray (CMA)

A

Flourescently labeled sample DNA and control DNA are mixed and hybridized to an array; visualization of the array gives information about the spots/color intensities for each probe, which correspond to variation in degrees of expression

Advantages: allows investigation of the whole genome simultaneously, reveals duplications and deletions

Limitations: detects gains & losses ONLY, not balanced rearrangements or SNPs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Heritability

A

The proportion of total variance in a trait that is due to variation in genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Allelic Heterogeneity

A

Different alleles in the same gene resulting in the same trait; OR, different alleles in the same gene resulting in different traits

Ex: Many mutations in the CFTR gene (alleles) lead to CF; different “classes” of alleles lead to different presentation of disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Locus Heterogeneity

A

Variants in different genes result in similar clinical presentation

Ex: Early onset Alzheimer’s results from mutations in 3 separate genes, all of which contribute to accumulation of AB42

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Loss of Function Mutations - 5 Examples

A

Duchenne Muscular Dystrophy (DMD gene, dystrophin)

Alpha Thalassemia (alpha thalassemia gene, a-globin)

Turner Syndrome (loss of X chromosome)

HNPP (PMP-22 gene, peripheral myelin protein)

OI Type I (Col1A1 gene, COL1A1 type collagen)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Gain of Function Mutations - 4 Examples

A

Hb Kempsey (B-globin gene)

Achondroplasia (FGFR3 gene)

Alzheimer Disease in Trisomy 21 (APP gene)

Charcot-Marie Tooth (PMP 22 gene)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Novel Property Mutations - 2 Examples

A

Sickle Cell Disease (B-globin)

Huntington Disease (CAG repeats/polyglutamine tracts lead to novel toxicity of protein)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Compound Heterozygote

A

An individual who carries two different mutant alleles of the same gene

Ex: HbS/HbC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Replicative Segregation

A

During cell division, the multiple copies of mtDNA in each of the mitochondria in a cell replicate and sort randomly among the newly synthesized mitochondria, which are distributed randomly between the two daughter cells

Daughter cells may be homoplasmic (a daughter cell with a pure population of WT mtDNA) or heteroplasmic (a daughter cell with a mixture of WT and mutant mtDNA)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

SINES & LINES

A

Short Interspersed Nuclear Elements (SINES) - Ex: Alu Family; ~300bp repeats, 10% of genome

Long Interspersed Nuclear Elements (LINES) - Ex: L1 family; ~6kb repeats, 20% of genome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Alpha satellite repeats

A

171 bp repeat unit found near centromeric region of all human chromosomes; likely important for chromosome segregation in mitosis and meiosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Candidate gene association study

A

Markers within a candidate gene are identified and allele frequences are compared in cases vs. controls; association implies linkage disequilibrium with a causal mutation

Disadvantages: Cases & controls must be ethnically matched, population stratification may lead to false positives

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Microsatellites & Short Tendem Repeat Polymorphisms (STRPs)

A

Repetitive DNA sequences 2-4 nucleotides long; short tandem repeat polymorphisms (STRPs) are different alleles that result from variation in the number of repeat units within a microsatellite region

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Mini-satellites & Variable Number Tandem Repeats

A

Repetitive DNA sequences 10-100 nucleotides long; variable number tandem repeats (VNTRs) are different alleles that result from variation of the number of repeat units within a minisatellite region

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Copy Number Polymorphisms (CNPs)

A

Recurring deletions or insertions of larger section of a chromosome, leading to gaps or duplications; may give rise to two discreet alleles (due to presence or absence of the chromosomal region) or to multiple alleles (due to variation in copy number of the chromosomal region)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Genome-Wide Association Studies (GWAS)

A

Same as candidate gene case-control association study but tests MANY markers across the genome searching for significantly different allele frequencies in cases vs. controls

Advantages: Can identify many genes, some new, that contribute to disease

Disadvantages: Requires a larger sample size (>1,000) to correct for multiple testing problem

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Chromosomal Analysis

A

Detects gross anomalies in chromosome number as well as large structural rearrangements (deletions, insertions, etc.)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

FISH

A

Flourescence In-situ hybridization; flourescently labeled, locus-specific probe can identify micro-deletions or multiple copies of loci of interest in patient DNA

Detects chromosomal microdeletion, microduplication, chromosomal rearrangements, and gene copy numbers of a known loci of interest

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Single Nucleotide Polymorphism (SNPs)

A

A difference in a single DNA nucleotide base, within a particular gene, that gives rise to 2 discreet alleles; SNPs occur at a rate of ~ 1 per 1,000 nucleotides between any two individuals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Genetic Linkage Studies

A

Used to study genome segments that are disproportionately co-inherited along with disease to determine if the loci are linked; “multiplex” families with multiple cases of a disease are studied to determine the frequency of recombination events between two loci

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Viral approaches to gene therapy

A
  1. Retroviral; can accomodate up to 8kb of DNA but requires target cell division for integration of recombinant DNA into host genome (i.e. limited use in non-dividing cells)
  2. Adenoviral: can accomodate up to 35kb and infect dividing or non-dividing cell but may lead to strong immune response
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Non-viral approahces to gene therapy

A
  1. Naked DNA (i.e. cDNA with regulatory elements introduced in a plasmic)
  2. DNA packaged into liposomes
  3. Protein-DNA conjugates
  4. Artificial chromosomes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Reciprocal Translocations

A

An exchange of segments between non-homologous chromosomes; meiosis procedes through formation of a quadrivalent figure by one of three mechanisms: alternate (normal/balanced gametes), adjacent 1 and adjacent 2 (partial trisomy/monosomy gametes)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Meiosis Nondisjunction I and II

A

Nondisjunction during Meiosis I produces a gamete with 24 chromosomes including both the paternal and maternal homologues

Nondisjunction during Meiosis II produces a gamete with 24 chromosomes including both copies of either the maternal or paternal chromatids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Mosaicism

A

Two or more chromosome complements are present within an individual; most often numerical, resulting from non-disjunction in an early postzygotic mitotic (somatic) division producing two different surviving cell lines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Robertsonian Translocation

A

Fusion of two acrocentric chromosomes near the centromere with loss of the short arms; may segregate via a trivalent structure along 3 pathways to produce normal/balanced gametes or partially trisomic/monosomic gametes

*Considered a balanced translocation because only repetitive DNA coding for rRNA is lost

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Maternal Age Effect (Two Hit Model and Cohesin Model)

A

Two Hit Model: Diminished meiotic recombination caused by a lack of chiasmata or mislocated chiasmata, followed by faulty segregation

Cohesin Model: Degradation of cohesin complexes throughout the course of extended Meiosis I arrest in oocytes, allowing “terminalization” of chiasmata and premature separation of homologs and/or sister chromatids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Paracentric vs. Pericentric Inversions

A

Paracentric: Inversions of a region of a chromosome excluding the centromere; crossover may generate both dicentric and acentric chromosomes in gametes

Pericentric Inversions: Inversions of a region of a chromosome including the centromere; crossover may result in chromosomes with duplications & deletions in gametes

*Balanced Rearrangements

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Paracentric vs. Pericentric Interstitial Deletion

A

Paracentric: Produces one chromosome with lost genetic material in the region of the deletion and one acentric fragment that is not transmissible

Pericentric: Produces two acentric fragments that are not transmissible and one stably transmissible centric ring (marker) chromosome

*Unbalanced rearrangements

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Isochromosome

A

An acrocentric chromosome in which the short arm is missing and the long arm is duplicated; may result from exchange between one arm of a chromosome and it’s homolog or by misdivision through the centromere in Meiosis II

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Uniparental disomy

A

Most often occurs as a result of trisomy followed by loss of the extra chromosome leaving either 2 maternal or 2 paternal homologs, where normal development is dependent on the expression of genes at the missing loci

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Gametes of a reciprocal translocation carrier - Adjacent-1 pathway

A

Adjacent-1 pathway leads to the formation of two unbalanced gametes with segregated homologs; following fertilization, each gamete will be partially trisomic & partially monosomic for one of the chromosomes involved in the translocation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Gametes of a reciprocal translocation carrier - Adjacent-2 pathway

A

Adjacent-2 leads to the formation of two unbalanced gametes in which homologous centromeres are unsegregated; following fertilization, each gamete will be partially trisomic & partially monosomic for one of the chromosomes involved in the translocation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

X inactivation

A

XIST gene is located within the X inactivation center on Xq and expressed only on the inactive X; XIST produces a non-coding RNA which associates in cis to signal DNA methylation and histone modification leading to expanded CpG methylation of the promoters of many (85-90%) genes on the inactive X chromosome

X inactivation is usually random, except for in the case of a damaged X chromosome (preferentially inactivated) or an X:autosomal translocation (preferentially remains active)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Mesonephric (Wolffian) ducts

A

Thickenings of the genital ridges that give rise to the epididymal duct and ductus deferens under the influence of androgens secreted by Leydig cells in the testes

38
Q

Sertoli cells

A

In the embryonic testes, produce Mullerian Inhibitory Substance (MIS) hormone that suppresses formation of the paramesonephric ducts

39
Q

SRY

A

Sex determining region of Y; lies near the pseudo-autosomal boundary of the Y chromosome and encodes a TF that is crucial for proper testes development

40
Q

Paramesonephric (Mullerian) ducts

A

Thickenings of the genital ridges that give rise to the female duct system (fallopian tubes, uterus, and upper vagina) in the absence of male hormonal signals (MIS and testosterone)

41
Q

DAX1

A

Located on Xp, encodes a TF that is dosage-sensitive in affecting gonadal sex; duplication of DAX1 suppresses the normal male-determining function of SRY and ovarian development results

Duplication of DAX1 can lead to XY sex reversal

42
Q

SOX9

A

Located on 17, required for normal testes formation; in it’s absence, testes fail to form; duplicated copies lead to XX sex reversal (phenotypic males in the absence of SRY)

Deletions lead to camtomelic dysplasia, a disease of skeletal malformation also characterized by XY sex reversal (phenotypic females)

43
Q

Androgen insensitivity syndrome

A

X-linked mutation of the AR gene which codes for the androgen receptor; individuals are XY but will present with phenotypically female genitalia; infants present with undescended testicles in the inguinal canal

44
Q

Congenital Adrenal Hyperplasia

A

Caused by mutation in the 21-hydroxylase enzyme which normally functions in the synthesis of glucocorticoids; precursors accumulate and are shunted toward the testosterone synthesis pathway leading to in-utero testosterone exposure

46 XX individuals present with ambiguous/masculinized genitalia

45
Q

Drug Metabolism - Phases I & II

A

Phase I - Attaches a polar group (usually a hydroxyl group) onto the compound to make it more soluble

Phase II - Attaches a sugar/acetyl group to detoxify the drug and make it easier to excrete

46
Q

Cytochrome P450

A

Liver & intestinal enzymes that participate in the Phase I metabolism (inactivation) of 90% of all commonly used medications; CYP3A4 is particularly active

Ex: CYP3A (Cyclosporin), CYP2D6 (Tricyclics, codeine), CYP2C9 (Warfarin)

47
Q

N-acetyltransferase (NAT) gene

A

NAT enzyme is important for Phase II metabolism; rate of acetylation is determined by polymorphism in the NAT genes

48
Q

Thiopurine methyltransferase (TPMT) gene

A

TPMT enzyme is important in the metabolism of 6-mercaptopurine and 6-thioguanine; giving children with deficient TPMT enzyme activity standard doses of ALL drugs will kill them by hyperimmunosuppression

49
Q

Vitamin K Epoxide Reductase Complex (VKORC1 gene)

A

VKORC1 protein reduces & recycles Vitamin K so that it can contribute to the carboxylation (activation) of clotting factors; deficient individuals are at greater risk for severe bleeds with anti-coagulants like Warfarin

50
Q

Patau Syndrome

A

Trisomy 13; characterized by severe intellectual disabilities, failure of the embryonic forebrain to divide properly (holoprosencephaly), facial clefts, polydactyly, renal anomalies, congenital heart & urogenital defects

51
Q

Edward’s Syndrome

A

Trisomy 18; characterized by receding jaw, low-set ears, intrauterine growth retardation, clenched fists, valvular heart disease, diaphragmatic hernia, renal anomalies

52
Q

Klinefelter Syndrome

A

47 XXY as a result of errors in either maternal meiosis I or II, or paternal meiosis I; characterized by tall stature, hypogonadism, gynecomastia, sterility, and learning disabilities

53
Q

Turner Syndrome

A

X0, most often resulting from loss of the paternal X chromosome; characterized by short stature, webbed neck, broad chest, ammenorrhea, renal & cardiovascular anomalies

54
Q

Hemophilia A

A

X-linked disorder of coagulation caused by mutation in the F8 gene which codes for clotting Factor VIII; characterized by spontaneous bleeding into joints, muscles, intracranial bleeding, and excessive bruising

55
Q

Hemophilia B

A

X-linked disorder of coagulation caused by mutation in the F9 gene which codes for clotting Factor IX

Hemophilia B-Leyden results from point mutations in the F9 promoter; affected males produce only 1% of the normal amount of Factor IX until puberty, when production increases to 60% normal

56
Q

Chromosomal abnormalities underlying Down Syndrome

A

Trisomy 21, usually as a result of maternal nondisjunction (95%)

Robertsonian translocation between 21q and the long arm of one of the other acrocentric chromosomes; 46 chromosomes but effectively trisomic for genes on 21q (4%)

Isochromosome 21 resulting from a 21q21q translocation; all gametes are either monosomic (lethal) or trisomic (Down)

Mosaic - cell populations have both normal and Trisomy 21 karyotype (1-2%)

57
Q

Neurofibromatosis Type I

A

Autosomal dominant condition resulting from loss of function mutation in the NF1 gene, which codes for neurofibromin tumor suppressor protein

Example of pleiotropy: characterized by growth of benign fleshy tumors (neurofibromas), cafe au lait spots, & freckling of the axillary & inguinal regions

58
Q

XYY Syndrome

A

Results from paternal nondisjunction at meiosis II, producing YY sperm; generally indistinguishable from XY males except for slight learning disability

59
Q

Trisomy X

A

XXX resulting from errors in maternal meiosis I; two of the X chromosomes are inactivated and so individual are phenotypically normal; may exhibit slight learning disability

60
Q

Charcot Marie Tooth

A

Autosomal dominant disorder caused by a duplication of the PMP-22 gene on chromosome 17; characterized by muscle atrophy of the foot, lower leg, and hand muscles, hammertoe; causes peripheral nerve demyelinating neuropathy

61
Q

Hereditary Neuropathy with Predisposition to Pressure Palsy (HNPP)

A

Autosomal dominant condition resulting from deletion of PMP-22 gene on 17; presents as focal pressure neuropathy

62
Q

Prader Willi Syndrome

A

Caused by deletion of 15q11-13 on the paternal homolog (or by uniparental disomy of the maternal homolog); characterized by almond-shaped eyes, excessive & indiscriminate eating, obesity, short stature, strabismus & nystagmus, hypotonicity, and mild to moderate cognitive disability

63
Q

Angelman Syndrome

A

Caused by deletion of 15q11-13 on the maternal homolog; characterized by short stature, spasticity, seizures, autism, and intellectual disability

64
Q

Acute Promyelocytic Leukemia (PML)

A

Characterized by translocation involving the retionic acid receptor-alpha (RARA) gene on 17 and the promyelocytic leukemia (PML) gene on 15; PML-RARa fusion protein binds to the RAR element in the promoters of certain genes necessary for proper myeloid differentiation

Treatment: Differentiation therapy with retinoic acid (vitamin A)

65
Q

Chronic Myeloid Leukemia (CML)

A

Characterized by translocation between the breakpoint cluster region (BCR) gene on 22 with the ABL gene on 9 - the “Philadelphia chromosome”; this translocation produces the BCR-ABL fusion protein, a constitutively active tyrosine kinase, leading to myeloproliferative disease

Treatment: Gleevac (a tyrosine kinase inhibitor)

66
Q

Down Syndrome Phenotypic Features

A 
Flattened facial features
Upslanting palpebral fissures
Epicanthal folds
Small Ears
Low muscle tone/ increased joint mobility 
Transverse Palmar Crease
67
Q

Medical issues associated with Down Syndrome

A 
Cardiac anomalies (30-50%), especially atrioventricular septum defects
Esophageal/duodenal atresia 
Hirschprung Disease
GERD
Nystagmus
Cataracts
Chronic ear infections & nasal congestion 
Obstructive apnea 
Thyroid disease (hypothyroidism) 
Increased risk of leukemia
Early onset Alzheimer's
68
Q

Fragile X Syndrome

A

Caused by an expansion in the number (>200) of CGG repeats in the 5’ UTR of the FMR1 gene, causing excessive methylation of the promoter and failure to express the FMR1 protein; characterized by intellectual disability, dysmorphic features, and autistic behavior

Genetic anticipation through the maternal germ line

Fragile X associated tremor/ataxia syndrome (FXTAS): X linked pre-mutation triplet repeat expansion (59-200 CGG) in FMR1 gene; characterized by adult onset ataxia, tremor, memory loss, peripheral neuropathy

69
Q

Acute Lymphoblastic Leukemia (ALL)

A

Caused by translocation between the TCF3 gene on 1 and the PBX1 gene on 19; Hyperdiploidy (>51 chromosomes) is associated with a good prognosis

70
Q

Cystic Fibrosis

A

Autosomal recessive disease caused by mutation in the CFTR gene causing build up of thick mucus secretions in the lung and pancreas

Ex: of allelic heterogeneity: mild/mild or mild/severe alleles lead to 15% pancreatic insufficiency whereas severe/severe alleles lead to 85% insufficiency

71
Q

Phenylketonuria (PKU)

A

Autosomal recessive condition resulting from defect in the phenylalanine hydroxylase (PAH) gene, a liver enzyme that catalyzes the breakdown of Phe; 1-3% have normal PAH but are defective in genes needed for the synthesis of BH4, a cofactor for PAH

PKU presents as microcephaly, seizure, tremor, gait disorders, and cognitive disability, as well as high plasma [Phe] and low plasma [Tyr]

72
Q

Maternal PKU & PKU testing

A

Pregnant women with PKU have increased risk of miscarriage/congenital malformation, cognitive disability, and growth impairment (regardless of fetal genotype) due to elevated Phe levels in maternal circulation; these women should be maintained on a low-Phe diet

Bacterial growth in Guthrie test is diagnostic for PKU

73
Q

alpha 1 antitrypsin deficiency (ATD)

A

Autosomal recessive disaese caused by mutation in the SERPINA1 gene, which codes for a serine protease inhibitor that targets elastase; if left uninhibited, elastase can destroy the connective tissue proteins in the lung, causing emphysema; misfolded protein also builds up in the liver, causing liver cirrhosis/carcinoma

Ex of allelic heterogeneity, with Z/Z genotype being the most severe and S/S genotype being the most mild

74
Q

Tay Sach’s Disease

A

Autosomal recessive disorder caused by HEXA gene mutation, which codes for the alpha subunit of hexosaminidase A (HexA), a heterodimer of alpha and beta subunits; HexA is needed to metabolize GM2 ganglioside; GM2 accumulates in the lysosomes of CNS neurons causing neurodegeneration

Symptoms present around 3-6 months: muscle weakness, seizures, vision/hearing loss, diminishing mental function, and death by 3-4 years

Fetuses can be screened by amniocentesis in utero

75
Q

A-B Variant of Tay Sachs

A

Rare form of T-S in which both HexA and HexB are notmal but GM2 accumulates due to a defect in the GM2 activator protein (GM2-AP) which facilitates interaction between the lipid substrate GM2 and the HexA enzyme

76
Q

Sickle Cell Anemia (HbSS)

A

Autosomal recessive condition caused by a missense mutation in the B-globin gene resulting in a Glu –> Val substitution; HbS is 80% less soluble than HbA and polymerizes into long fibers that distort the RBC

HbS can be diagnosed by digestion with restriction enzyme MstII yielding only one 1.35kb fragment or by hemoglobin electrophoresis

Heterozygotes are phenotypically normal except under conditions of low pO2

77
Q

Hemoglobin C Disease (HbC)

A

Autosomal recessive condition caused by a missense mtuation in the B-globin gene resulting in a Glu –> Lys mutation; HbC is less soluble than HbA and forms crystals that reduce the deformability of the RBC

78
Q

a-Thalassemias

A

Anemic disorders caused by deletion of one or both copies of the a-globin gene on the a-cluster of chromsome 16

79
Q

a-Thalassemia alleles

A

a-thal-1-allele is caused by deletion of both copies of a-globin genes; homozygotes (–/–) are stillborn whereas heterozygotes (aa/–) have a-thalassemia trait (mild anemia); allele common in SE Asia

a-thal-2 allele is caused by deletion of only one copy of a-globin gene in the cluster; homozygotes (a-/a-) have a-thalassemia trait and heterozygotes (aa/a-) are phenotypically normal; allele is common in Africa, Meditteranean, and Asia

80
Q

HbH Disease

A

Caused by compound heterozygosity for a-thal-1 and a-thal-2 alleles (a-/–); individuals produce only 25% of the normal a-globin levels, resulting in severe anema; marrow compensates by producing higher levels of HbH (B4) which precipitates and may lead to hydrops fetalis (edema)

81
Q

Categorizations of B-thalassemia

A

Thalassemia Major (Cooley’s Anemia): genotype (-/-) leading to severe anemia; patients are treated with transfusion & iron chelation

Thalassemia Intermedia: mild-moderate anemia caused by inheritance of 2 abnormal b-globin genes

Thalassemia minor: clinically insignificant anemia caused by genotype (b/-)

Simple B-thalassemia: only b-globin genes are affected

Complex B-thalassemia: b-globin genes AND other genes on the B-cluster are affected

B+ thalassemia: some B-globin is made and some HbA is present

B- thalassemia: No b-globin is made and no HbA is present; Hb present at <5% normal levels and is mostly a2y2 and a2d2 variants; mostly lethal

82
Q

Hereditary Persistent Fetal Hemoglobin (HPFH)

A

Caused by deletions in the promoter region of the b-globin gene OR by large deletions in the B-cluster including d- and B-globin genes; 100% of Hb is HbF (a2y2) which is usually phenotypically normal

*Heterochronic mutation mechanism

83
Q

Duchenne Muscular Dystrophy (DMD)

A

X-linked recessive disorder caused by mutation of DMD gene coding for dystrophin protein; boys present with calf hypertrophy, abnormal gait at 3-5 years with progressive involvement of respiratory muscles and death around 18 years

DMD-associated cardiomyopathy: Weakening & enlargement of the heart as a result of a lack of dystrophin in the myocardium; usually presents between 20-40 years of age without skeletal muscle involvement

84
Q

Osteogenesis Imperfecta Types I & II

A

OI Type I: Autosomal dominant condition caused by mutation in the COL1A1 gene; normal collagen trimers are made in reduced amounts; patients present with brittle bones, increased fractures, blue sclerae

OI Type II: Caused by mutation in COL1A2 gene leading to production of protein with an abnormal (novel) structure; half of collagen triple helices will incorporate this abnormal protein and produce an abnormal collagen trimer, leading to severe phenotype, often fatal

85
Q

Hb Kempsey & Hb Kansas

A

Hb Kempsey: Missense mutation in the b-globin gene that prevents T/R switching; Hb remains “locked” in the R state which has higher O2 affinity and cannot unload O2 in the tissues, leading to production of more RBCs (polycythemia)

Hb Kansas: Hb remains locked in the low O2 affinity “T state” leading to low O2 levels in the tissues presenting as cyanosis

86
Q

Huntington Disease

A

Autosomal dominant disorder characterized by > 40 CAG coding repeats and expanded polyglutamine tracts in the HTT gene on 4 coding for Huntingtin protein; the number of repeats corresponds to absence, presence, and severity of the disease and genetic anticipation occurs through the paternal line

87
Q

Myotonic Dystrophy

A

Autosomal dominant condition caused by expanded CTG repeats in the 3’ region of the DMPK gene, leading to production of abnormal RNA; characterized by facial weakness, ptosis (eyelid drooping); genetic anticipation occurs through the maternal line

88
Q

Achondroplasia

A

Autosomal dominant disorder caused by gain of function mutation in FGFR3; constitituve activation of this tyrosine kinase receptor inhibits chondrocyte proliferation within the growth plate

Characterized by rhizomelic shortening of the limbs, midface hypoplasia, 10% risk of brainstem compression

Spontaneous mutations occur in the father’s germline and increase in frequency with advanced paternal age

89
Q

Marfan syndrome

A

Autosomal dominant condition caused by mutation in the FBN1 gene coding for fibrillin, an ECM protein component of connective tissue; characterized by tall stature, mitral valve prolapse, and aortic dilation/rupture

90
Q

Polycistic Kidney Disease (PKD)

A

Autosomal dominant condition caused by mutation in PDK1 or PDK2 encoding polycistin protein; characterized by bilateral renal & hepatic cysts & progressive renal failure

Ex: of locus heterogeneity

91
Q

Familial Hypercholesterolemia

A

Autosomal dominant condition resulting from mutation in the LDLR gene; LDL deposits in the coronary arteries (atheromas) and in the skin and tendons (xanthomas)

92
Q

Fabry Disease

A

X-linked disorder caused by mutation in the alpha-galactosidase A enzyme leading to lipid accumulation; presents with microvascular disease, neuropathy, nephropathy, cardiomyopathy

M2M Final Exam (9 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions