Sparsh Gupta genetic
The mother has sickle cell disease; Father is normal;Chances of children having sickle cell disease andsickle cell trait respectively are: (a) 0 and 100% (b) 25 and 25% (c) 50 and 50% (d) 10 and 50%
(a) 0 and 100% Sickle cell anemia is an autosomal recessive disorder.• Sickle cell disease is the homozygous state of HbS (SS) where S stands for gene coding HbS.• Sickle cell trait is the heterozygous state of HbS (SA) where A stands for absent gene.• Normal individual has no gene for HbS (AA)If the mother has sickle cell disease 'SS' and father is normal 'AA' all the offsprings will be 'SA'. Thus % of sickle cell disease (SS) will be zero and that of sickle cell trait (SA) will be 100%
Which of the following is true of Klinefelter'ssyndrome: (a) Chromosome pattern in 47 XXY (b) Mental retardation is present (c) Hypogonadism occurs (d) Increased FSH level (e) Eunuchoid proportions
(a) Chromosome pattern is 47 XXY; (b) Mental retardation is present; (c) Hypogonadism occurs; (d) Increased FSHlevel; (e) Eunuchoid proportions: Klinefelter's syndrome is defined as male hypogonadism that occurs when there are two or more X chromosomes or oneor more Y chromosomes
Autosomal recessive diseases are (a) Hereditary spherocytosis (b) Thalassemia (c) Sickle cell anemia (d) Cystic fibrosis (e) Hemophilia A
(b) Thalassemia; (c) Sickle cell anemia; (d) Cystic fibrosis Hereditary spherocytosis is an autosomal dominant disorder Hemophilia is an X-linked recessive disease. A broad generalization is that the physiologic metabolic enzyme deficiencies are all autosomal recessive whereas Structural defects are autosomal dominant.
Which of the following is/are an example/examples ofnon-Mendelian inheritance? (a) Genomic imprinting (b) Uniparental disomy (c) Mitochondrial inheritance (d) All of the above
) All of the above
Autosomal dominant disorders are all except (a) Hereditary spherocytosis (b) Thalassemia (c) Sickle cell anemia (d) Cystic fibrosis (e) Hemophilia
. (b) Thalassemia, (c) sickle cell disease, (d) cystic fibrosis, (e) hemophilia
Resolution provided by the various FISH techniques fiber FISH
1-300 bd
Resolution provided by the various FISH techniques pro metaphase spreads
1Mb
Resolution provided by the various FISH techniques. Metaphase spreads
2-3 Mb
Resolution provided by the various FISH techniques mechanically stretched chromosomes
200-3000 kb
In Down syndrome, there is non disjunction ofchromosome
21
Chromosomes are visualized through light microscopewith resolution of :(a) 5 Kb (b) 50 mb (c) 5 (d) 500 Kb
5mb Karyotype analysis detects both numerical and structural chromosomal aberrations (overall resolution is 5 Mega bases(Mb); breakpoint resolution is 5 to 15 Mb).
Achondroplasia
Autosomal Dominant
Neurofibromatosis is (a) Autosomal dominant (b) AR (c) X-linked recessive (d) All
Autosomal dominant
Adult polycystic kidney disease is inherited by :(a) Autosomal dominant (b) Autosomal recessive (c) X-linked (d) Mitochondrial
Autosomal dominant...
Karyotyping is done for: (a) Chromosomal disorders (b) Autosomal recessive disorders (c) Autosomal dominant disorders (d) Linkage disorders
Chromosomal disorders Karyotyping is the study of chromosomes• Chromosomes are arrested in metaphase by Colchicine• These are then stained by many stains. Most commonly used stain is Giemsa stain, so called G-banding• The chromosomes are arranged in order of decreasing length• Any alteration in number or structure of chromosomes can be easily detected by karyotyping
BRCA 1 gene is located on?
Chromosome 17
Osteogenesis imperfecta defect in:
Collagen type I Osteogenesis imperfecta (or brittle bone diseaseQ) is a phenotypically diverse disorder caused by deficiencies in thesynthesis of type 1 collagenQ.• It is the most common inherited disorder of connective tissue.• It principally affects bone, but also impacts other tissues rich in type 1 collagen (joints, eyes, ears, skin, and teeth)
A 26-year-old woman presents because of troublewith her vision. Physical examination reveals a verytall, thin woman with long, thin fingers. Examiningher eyes reveals the lens of her left eye to be in theanterior chamber. Her blood levels of methionine andcystathionine are within normal levels. Which of thefollowing is the most likely cause of this patient's signsand symptoms? (a) Abnormal copper metabolism (b) Decreased levels of vitamin D (c) Decreased lysyl hydroxylation of collagen (d) Defective synthesis of fibrillin (e) Defective synthesis of type I collagen
Defective synthesis of fibrillin The stem describes a patient of Marfan syndrome which is an autosomal dominant disorder that results from defective synthesis of fibrillin.
Which of the following is not X linked condition: (a) Duchenne muscular dystrophy (b) Emery-Dreifuss muscular dystrophy (c) Facioscapulohumeral muscular dystrophy (d) Becker muscular dystrophy
Facioscapulohumeral muscular dystrophy Facioscapulohumeral muscular dystrophy is an autosomal dominant disorder characterised by facial weakness (difficulty with eye closure and impaired smile) and scapular winging.
Which of the following is an autosomal dominantmetabolic disorder? (a) Cystic fibrosis (b) Phenylketonuria (c) a-1 antitrypsin deficiency (d) Familial hypercholesterolemia
Familial hypercholesterolemia (Ref: Robbins 7th/152, 9/e p Most of the metabolic disorders have autosomal recessive inheritance except: Her - Her's disease [Liver phosphorylase deficiency] Left - Lesch Nyhan syndrome Eye - Ocular albinism Has - Hunter syndrome and Hypercholesterolemia (familial) Five - Fabry's disease Pimples - Porphyria [Acute intermittent] All these exceptions have X linked recessive inheritance except acute intermittent porphyria and familial hypercholesterolemia which are autosomal dominant disorders.
In Marfan's syndrome there is defect in protein (a) Collagen (b) Elastin (c) Fibrillin (d) All
Fibrillin
Differential expression of same gene depending onparent of origin is referred to as:
Genomic imprinting is the phenomenon that leads to preferential expression of an allele depending on its, parental origin. It is also seen in Wiedmann syndrome (have two paternal but no maternal copies of chromosome 11).• Albright's hereditary osteodystrophy (short stature, brachydactyly and PTH resistance). There is mutation in the Gs a subunit;individuals express the disease only when the mutation is inherited from the mother).
Blue black pigmentation in alkaptonuria is due to (a) Homogentisic acid (b) Oxalic acid (c) Glucouronic acid (d) All
Homogentisic acid
All of the following are characterized by 'trinucleotiderepeats' affecting the non-coding regions exceptpeats' affecting (a) Friedrich's ataxia (b) Fragile X syndrome (c) Huntington's disease (d) Myotonic dystrophy
Huntington's disease Huntington's disease is characterized by trinucleotide repeats affecting the coding region. Rest all conditions mentionedin the options affects the non-coding regions.
Characteristics of Klinefelter syndrome
Hypogonadism comprising small, firm testes• Hyalinized seminiferous tubules • Failure of development of secondary sexual characters• Chromosomal analysis reveals 47XXY chromosomal pattern (classic form) or 47XY/47XXY mosaicism.• Mental retardation is seen.• Plasma FSH, and LH level elevated.• Plasma testosterone level averages half normal, plasma estradiol level elevated.• Eunuchoid proportions is seen.
Catastrophic variant of Ehler Danlos syndrome is (a) I (b) II (c) III (d) IV
IV
One of the following disorders is due to maternaldisomy (a) Prader Willi syndrome (b) Angelman syndrome (c) Hydatidiform mole (d) Klinefelter's syndrome
Klinefelter's syndrome Maternal disomy is associated with disorders like Prader-Willi syndrome and Angelman syndrome. It is also seen in otherconditions like molar pregnancy and Beckwith-Wiedemann syndrome.
NARP syndrome is seen in: (a) Mitochondrial diseases (b) Glycogen storage diseases (c) Lysosomal storage diseases (d) Lipid storage diseases
Mitochondrial Disorder NARP syndrome (Neuropathy, ataxia, and retinitis pigmentosa), is a condition related to changes in mitochondrial DNA.
Mitochondrial DNA (mt-DNA) is known for all except :(a) Maternal inheritance (b) Heteroplasmy (c) Leber hereditary optic neuropathy is the prototype (d) Nemaline myopathy results due to mutations in mtDNA
Nemaline myopathy results due to mutations in mt-DNA Nemaline myopathy is not a mitochondrial disease Nemaline myopathy is a clinically heterogeneous condition and not a mitochondrial disease. Five genes have been associated with thismyopathy. All code for thin filament-associated proteins, suggesting disturbed assembly or interplay of these structures as a pivotalmechanism. Mutations of the nebulin (NEB) gene account for most cases, including both severe neonatal and early childhood forms,inherited as autosomal recessive disorders.
Genomic imprinting is associated with :(a) Silencing of paternal chromosome (b) Silencing of maternal chromosome (c) Angelman syndrome (d) Prader Willi syndrome (e) Gonadal mosaicism
Silencing of paternal chromosome; (b) Silencing of maternal chromosome; (c) Angelman syndrome; (d) Prader Willi syndrome
Karyotype is:
Size, shape and number of chromosome
Patient present with skin bullae on sun exposure. Thereis a defect in which of the following? (a) Thymidine dimers (b) Trinucleotide repeats (c) Sugar changes (d) DNA methylation
Thymidine dimers
In Huntington chorea the causative mutation in theprotein huntingtin is a (a) Point mutation (b) Gene deletion (c) Frameshift mutation (d) Trinucleotide repeat expansion
Trinucleotide repeat expansion Expansion of trinucleotide repeats is an important genetic cause of human disease, particularly neurodegenerativedisorders. There are three key mechanisms by which unstable repeats cause diseases:• Loss of function of the affected gene occurs in fragile X syndrome. In such cases the repeats are generally in noncoding part of the gene.• A toxic gain of function by alterations of protein structure as in Huntington disease and spinocerebellar ataxias. Insuch cases the expansions occur in the coding regions of the genes.• A toxic gain of function mediated by mRNA as is seen in fragile X tremor-ataxia syndrome. In this condition, thenon coding parts of the gene are affected.
Increasing severity of mental retardation in malemembers over generations is a result of: (a) Mitochondrial DNA mutation (b) Frameshift mutation (c) Y linked disorder (d) Trinucleotide repeat mutation
Trinucleotide repeat mutation
Patau syndrome is due to which of the following?
Trisomy 13 Trisomy 13 is known as Patau syndrome characterized by:• Mentalretardation, rocker bottom feet and congenital heart defects (VSD and PDA)• Cleft lip/palate• Polydactyly• Microcephaly• Eye defects (microphthalmia, iris coloboma, cataract, retinal dysplasia)• Capillary hemangiomata p for Patau and polydactyly as well as palate defects: Patau syndrome (trisomy 13)• Edward syndrome (trisomy 18): e for EdwardandExtra occiput (prominent occiput)
Kinky hair disease is a disorder where an affected childhas peculiar white stubby hair, does not grow, braindegeneration is seen and dies by age of two years.Mrs. A is hesitant about having children because hertwo sisters had sons who had died from kinky hairdisease. Her mother's brother also died of the samecondition. Which of the following is the possible modeof inheritance in her family? (a) X-linked recessive (b) X-linked dominant (c) Autosomal recessive (d) Autosomal dominant
X - linked Recessive The given disease is manifesting only in males, therefore it is sex-linked disease. Females are not affected, so they must becarriers. This is a classical inheritance feature of X-linked recessive disorder. Remember:• Male is having XY, i.e. only X-chromosome. So, even if one mutant allele is present on X-chromosome, it will manifest(whether recessive or dominant).• Females are XX, so if one gene is mutated in X-chromosome, female will be phenotypically normal and genotypically carrier, ifinheritance is recessive but female will suffer from disease, if it is X-linked dominant.• There is no sex predilection in autosomal dominant or recessive disorders.
Hemophilia is associated with :(a) X chromosome (b) Y Chromosome (c) Chromosome 3 (d) Chromosome 16
X chromosome...
Duchenne muscular dystrophy is inherited as: (a) X linked (b) Autosomal dominant (c) Autosomal recessive (d) Codominant
X linked
Red green colour blindness
X linked recessive
Males are more commonly affected than females inwhich of the following genetic disorders?(a) Autosomal Recessive Disorder (b) Autosomal Dominant Disorder (c) X-linked Recessive Disorder (d) X-linked Dominant Disorder
X-linked Recessive Disorder Analysis of X linked recessive disorders Males have an X and a Y chromosome. There is no corresponding locus for a mutant allele of the X chromosome on the Ychromosome. The mutant recessive gene on the X chromosome expresses itself in a male child because it is not suppressed bya normal allele whereas in the female, the presence of a normal allele on other X-chromosome prevents the expression of thedisease so, females only act as carriers.Q
Duchenne dystrophy is a: (a) Autosomal dominant disorder (b) X-linked dominant disease (c) Autosomal recessive disease (d) X-linked recessive disease
X-linked recessive disease
No change of genetic material occurs in which of thefollowing cytogenetic abnormalities? (a) Deletion (b) Insertion (c) Translocation (d) Inversion
d) Inversion Inversion refers to a rearrangement that involves two breaks within a single chromosome with reincorporation of theinverted, intervening segment. It can be of the following two types: a. An inversion involving only one arm of the chromosome is known as paracentric .b. If the breaks are on opposite sides of the centromere, it is known as pericentric.Inversions are often fully compatible with normal development. It is not associated with change in genetic material.• Deletion refers to loss of a portion of a chromosome. Similarly, insertion would lead to increase (and not loss) in thegenetic material.• In a translocation, a segment of one chromosome is transferred to another. It can be of the following types:- In balanced reciprocal translocation, there are single breaks in each of two chromosomes, with exchange of material.There is no loss of genetic material and so, the affected individual is likely to be phenotypically normal.A balanced translocation carrier, however, is at increased risk for producing abnormal gametes.- In robertsonian translocation (or centric fusion), a translocation between two acrocentric chromosomes. Typically the breaks occur close to the centromeres of each chromosome. Transfer of the segments then leads to onevery large chromosome and one extremely small one. Usually the small product is lost. This loss is compatiblewith a normal phenotype because it carries only highly redundant genes. Therefore, deletion, insertion and Robertsonian translocation would lead to change in genetic material.
Y-chromosome is
Acrocentric X chromosome is Submetacentric and Y chromosome is Telocentric.
Which one is not a feature of cystic fibrosis? (a) Autososmal recessive disease (b) Abonormal chloride transport (c) Affects intestine only (d) Increased risk of pulmonary infections
Affects intestine only Cystic fibrosis is also known as salty baby syndromeQ or mucoviscidosisQ. It is an autosomal recessiveQ geneticdisorder that affects most critically the lungs, and also the pancreas, liver, and intestine.• It is characterized by abnormal transport of chloride and sodium across epithelium, leading to thick, viscous secretions• Affected patients are prone to Pseudomonas infectionsQ for which a combination of 3rd generation cepahalosporinsand aminoglycosideQ is used.• The most commonly used form of testing is the sweat test using the drug that stimulates sweating (pilocarpineiontophoresisQ).• Patients require repeated use of antibiotics and lung transplantation (in later stages) to survive.
All are autosomal dominant disorders except (a) Albinism (b) Marfan's syndrome (c) Familial adenomatous polyposis (d) Von-Hippel Lindau syndrome
Albinism
Gene therapy is used for: (a) Cystic fibrosis (b) Sickle cell anemia (c) Thalassemia (d) All of the above
All of the above Gene transfer is a novel area of therapeutics in which the active agent is a nucleic acid sequence rather than a protein orsmall molecule. Most gene transfers are carried out using a vector or gene delivery vehicle because delivery of naked DNA or RNA to a cell is an inefficient process. More clear-cut success has been achieved in a gene therapy trial for another formof SCID, adenosine deaminase (ADA) deficiency. Other diseases likely to be amenable to transduction of hemaopietic stemcells (HSCs) include• Wiskott-Aldrich syndrome• Chronic granulomatous disease• Sickle cell disease• Thalassemia. Clinical trials using recombinant adeno-associated vectors are now ongoing for muscular dystrophies, alpha-1 antitrypsindeficiency, lipoprotein lipase deficiency, hemophilia B, and a form of congenital blindness called Leber's congenital amaurosis.
Genomic imprinting is seen in - (a) Klinefelter's syndrome (b) Down's syndrome (c) Angelman syndrome (d) Hydatidi form mole
Angelman syndrome Imprinting is a process associated with selective inactivation of either the maternal or paternal allele. Thus, maternal imprinting refersto transcriptional silencing of the maternal allele, whereas paternal imprinting implies that the paternal allele is inactivated. Imprinting occurs in the ovum or the sperm, before fertilization, and then is stably transmitted to all somatic cells throughmitosis . The genomic imprinting is best illustrated by the following disorders: Prader-Willi syndrome and Angelmansyndrome
45-year-old male Arvind who was previouslydiagnosed with depression is now experiencinginvoluntary grimacing and strange movements of hisarms and legs. Neurological examination shows normalstrength and normal deep tendon reflexes. No sensorydeficits are noted. The patient's grandfather died of aneurological disease at 65 years old, and the patient'sfather died of a similar disease at 58. This patient hasan earlier onset of disease than either his father orgrandfather is most likely explained by which of thefollowing? (a) Increased penetrance (b) Pleiotropy (c) Anticipation (d) Mosaicism
Anticipation Huntington disease manifests with the triad of movement disorder (chorea), behavioral abnormalities aggressiveness,apathy or depression), and dementia. Huntington disease is transmitted as an autosomal dominant trait with 100%penetrance, meaning that if a child inherits the abnormal gene, that child will inevitably develop Huntington disease. Mostpatients develop symptoms in their 40s or 50s. An earlier age of onset is associated with a larger number of trinucleotiderepeats. During spermatogenesis, CAG repeats in the abnormal HD gene rapidly increase. Thus, patients who receivean abnormal gene from their fathers tend to develop the disease earlier in life. (The number of trinucleotide repeats onHD gene remains the same during maternal transmission.) The tendency for clinical symptoms to worsen and/or occurearlier in subsequent generations is called anticipation. Anticipation is common in disorders associated with trinucleotide repeats as in Fragile X syndrome, myotonic dystrophy and Friedreich ataxia.• (Choice A) The transmission of an abnormal gene from a parent to a child does not always cause disease. The likelihood that theproperties of a gene will be expressed is called penetrance. Huntington disease is a disorder with 100% penetrance means allindividuals who have an abnormal HD gene will develop Huntington disease.• (Choice B) Sometimes, one gene mutation leads to multiple phenotypic abnormalities, a genetic phenomenon named "pleiotropy." In Huntington disease, pleiotropy is present because the mutation of one gene (HD) causes dysfunction of behavior, movementand cognition.• (Choice D)The presence of two populations of cells with different genotypes in one patient is called mosaicism. Examples includemilder forms of Turner (genotype 46XX/45X0), Klinefelter (46XY/47XXY), and Down syndromes.
Which of the following is an autosomal recessivecondition? (a) Ataxia telangectasia (b) Peutz Jeghers syndrome (c) Neurofibromatosis (d) Tuberous sclerosis
Ataxia telangectasia Ataxia telangiectasiais an autosomal recesive condition. Patients have increased sensitivity to x-ray-induced chromosome abnormalities. Characterized by an ataxic-dyskinetic syndrome beginning in early childhood, caused by neuronal degeneration predominantly in the cerebellum, the subsequent development of telangiectasias in the conjunctiva and skin, and immunodeficiency. The nuclei of cells in many organs (e.g., Schwann cells in dorsal root ganglia and peripheral nerves, endothelial cells as well as pituicytes) show a bizarre enlargement of the cell nucleus and are referred to as amphicytes. The lymph nodes, thymus, and gonads are hypoplastic. Clinical features include recurrent sinopulmonary infections and unsteadiness in walking. Increased risk of development of lymphoid malignant disease (T-cell leukemia and lymphoma All other options are autosomal dominant conditions.
Inheritance of Gardner syndrome is: (a) Autosomal recessive (b) Autosomal dominant (c) X linkeddominant (d) X linked recessive
Autosomal dominant It is a subtype of familial adenomatous polyposis inherited as an autososmal dominant disorder. Gardener syndrome Q Intestinal polyps + epidermal cysts + fibromatosis + osteomas (of the mandible, long bonesand skull).
Neurofibroma is having which of the followinginheritance? (a) Autosomal dominant (b) Autosomal recessive (c) X-linked recessive (d) X-linked dominat
Autosomal dominant...
Which of the following is the inheritance ofHuntington's chorea? (a) Autosomal dominant (b) Autosomal recessive (c) X-linked (d) Mitochondrial
Autosomal dominant...
Xeroderma pigmentosum
Autosomal recessiveQ inherited disorder of defective DNA repairQ.• Affected individuals are at increased risk for the development of skin cancers particularly following exposure to the UV light contained insun rays.• UV radiation causes cross-linking of pyrimidine residues, preventing normal DNA replication. Such DNA damage is repaired by thenucleotide excision repair systemQ.• Deficiency of enzymes like UV specific endonuclease (commonest), DNA polymerase and DNA ligase is implicated
Familial hypercholesterolemia
Autosomal rescessive
Which of the following tests is used to differentiate thechromosome of normal and cancer cells? (a) PCR (b) Comparative genomic hybridization (c) Western blotting (d) Karyotyping
Comparative genomic hybridization Comparative genomic hybridization (CGH) differentiates between cancer and normal cells.
Down's syndrome is associated with the clinicalmanifestation of mental retardation. Which of thefollowing is not associated with Down's syndrome? (a) Trisomy 21 (b) Mosaic 21 (c) Translocation t (14,21), t (21,21) (d) Deletion of 21
Deletion of 21 Down syndrome is characterized by trisomy 21 (NOT deletion of chromosome 21)
young man Ramkishore presents for an employmentphysical. He is very tall,has long fingers, andhyperflexible joints. He states that he has alwaysbeen called "double jointed". Which of the followingdisorders is associated with this syndrome? (a) Dissecting aortic aneurysm (b) Hepatosplenomegaly (c) Polycystic kidneys (d) Progressive neurologic dysfunction
Dissecting aortic aneurysm The patient has Marfan syndrome, an autosomal dominant disorder caused by a defect in the gene on chromosome 15 encoding fibrillin,a 350 kD glycoprotein. Fibrillin is a major component of elastin associated microfibrils, which are common in large blood vessels andthe suspensory ligaments of the lens. Abnormal fibrillin predisposes for cystic medial necrosis of the aorta, which may be complicatedby aortic dissection. Other features of the syndrome are subluxated lens of the eye, mitral valve prolapse, and a shortened life span(often due to aortic rupture).
Dominant negative inheritance is seen in: (a) Ehler Danlos syndrome (b) Marfan's syndrome (c) Hunter syndrome (d) Osteogenesis imperfecta (e) Hereditary retinoblastoma
Ehler Danlos syndrome; (b) Marfan's syndrome; (d) Osteogenesis imperfecta Dominant negative effects occurs when a mutant polypeptide not only loses its own function but also interferes withthe product of normal allele in a heterozygote, thus causing more severe effects than deletion or non-sense mutations inthe same gene. Structural proteins that contribute to multimeric structures are vulnerable to dominant negative effects, e.g.collagen. Seen in: Osteogenesis imperfecta, Ehler Danlos syndrome, Marfan's syndrome.
All of the following are chromosomal breakagesyndromes except (a) Fanconi's anemia (b) Ehler-Danlos syndrome (c) Bloom's syndrome (d) Ataxia telangiectasia
Ehlers-Danlos syndrome Chromosome breakage syndromes are associated with high level of chromosomal instability. Such conditions include. Fanconi anemia, Bloom syndrome and Ataxia telangiectasia. Ehlers-Danlos syndrome (EDS)• Genetic disorder resulting from defective synthesis of fibrillar collagen• Skin is extraordinary stretchable, extremely fragile and vulnerable to trauma, joints are hypermobile• Internal complications: rupture of colon, large arteries
Effective polymerase reaction was repeated for 3cycles on a DNA molecule. What will be the resultingformation of the copies?
Eight times Friends, the number of copies of the particle after 'n' cycles of polymerase chain reaction is given by the formula 2n timesthe original copies. So, the number of copies after 3 cycles would be 23 = 8 times the original copies. PCR is used to amplify DNA but RT - PCR (reverse transcriptase PCR) can be used for studying mRNA.
True statements about α-l anti-trypsin deficiency is (a) Autosomal dominant disease (b) Emphysema (c) Fibrosis of portal tract (d) Diastase resistant positive hepatocytes (e) Orcein positive granules
Emphysema; (c) Fibrosis of portal tact; (d) Diastase resistance positive hepatocytes; This is an autosomal recessive disease characterized by deficiency of a - antitrypsin (important protease inhibitor). There is portal tract fibrosis in neonatal hepatitis. About 10 - 20% of newborn with a - antitrypsin deficiency develop neonatal hepatitis and cholestasis. Hepatocellular carcinoma develops in 2-3 % a - antitrypsin deficiency in adults. The treatment and cure, for severe hepatic disease is orthotropic liver transplantation.
Which of the following techniques can be used to detectexact localisation of a genetic locus?
FISH FISH uses DNA probes that recognize sequences specific to particular chromosomal regions.. (Ref: Robbind 8/e p179 Bacterial artificial chromosomes that span the entire human genome were created. These DNA clones are labeled withfluorescent dyes and applied to metaphase spreads or interphase nuclei. The probe hybridizes to its homologous genomicsequence and thus labels a specific chromosomal region that can be visualized under a fluorescent microscope.
In marfan syndrome, the defect is in:
Fibrillin I Fibrillin occurs in two homologous forms, fibrillin-1 and fibrillin-2, encoded by two separate genes, FBN1 and FBN2mapped on chromosomes 15q21.1 and 5q23.31, respectively.• Mutations of FBN1 (affecting fibrillin-1Q) underlie Marfan syndrome• Mutations of the related FBN2 gene (fibrillin-2Q) are less common, and are associated with congenital contracturalarachnodactyly, an autosomal dominant disorder characterized by skeletal abnormalities.
In-situ DNA nick end labeling can quantitate: (a) Fraction of cells in apoptotic pathways (b) Fraction of cells in S phase (c) p53 gene product (d) bcr/abl gene
Fraction of cells in apoptotic pathways In situ DNA nick end - labeling is an in-situ method for detecting areas of DNA which are nicked during apoptosis. Terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) is a method for detecting apoptotic cells thatexhibit DNA fragmentation.
young boy, Rinku is being evaluated fordevelopmental delay, mild autism, and mentalretardation. Physical examination reveals the boy tohave large, reverted ears and a long face with a largemandible. He is also found to have macroorchidism(large testes), and extensive workup reveals multipletandem repeats of the nucleotide sequence CGG inhis DNA Which of the following is the most likelydiagnosis?
Fragile - X syndrome The presentation in the stem of the question is characteristic of Fragile X syndrome.
Which of the following procedures as routine techniquefor karyotyping using light microscopy? (a) C-banding (b) G-banding (c) Q-banding (d) Brd V-staining
G-Banding G banding is the most widely used technique for routine cytogenetic analysis.' So, G banding is chosen as the answer ofchoice.
Karyotyping most commonly done under lightmicroscopy:
G-banding Q banding is easily ruled out because it does not require light microscopy. Cancer cytogenetics clearly mentions that 'sequence specifictechniques like T banding; C banding and NOR banding have been replaced by in situ hybridization techniques. G banding is the mostwidely used technique for routine cytogenetic analysis.
Preferential expression of the gene depending upon theparent of origin is called: (a) Genomic imprinting (b) Mosaicism (c) Alleles (d) Chimerism
Genomic imprinting
A couple has two children affected with tuberoussclerosis. On detailed clinical and laboratory evaluation(including molecular studies) both parents are normal.Which one of the following explains the two affectedchildren in this family?(a) Non penetrance (b) Uniparental disomy (c) Genomic imprinting (d) Germline mosaicism
Germline mosaicism Germline mosaicism is seen with osteogenesis imperfecta and tuberous sclerosis.
Two siblings with osteogenesis imperfecta have normalparents. The mode of inheritance is explained by whichof the following? (a) Anticipation (b) Genomic imprinting (c) Germline mosaicism (d) New mutation
Germline mosaicism Gonadal mosaicism results from a mutation that occurs postzygotically during early (embryonic) development. If themutation affects only cells destined to form the gonads, the gametes carry the mutation, but the somatic cells of theindividual are completely normal. Such an individual is said to exhibit germ line or gonadal mosaicism. A phenotypicallynormal parent who has germ line mosaicism can transmit the disease-causing mutation to the offspring through themutant gamete. Since the progenitor cells of the gametes carry the mutation, there is a definite possibility that more thanone child of such a parent would be affected. It is seen with tuberous sclerosis and osteogenests imperfecta.
In Prader Willi syndrome, which of the following isincreased? (a) LH (b) FSH (c) TSH (d) Ghrelin
Ghrelin Ghrelin is a growth hormone secretagogue and the only gut hormone with orexigenic (means increasing food intake)property.• It is primarily produced in the stomach. In children, its value is inversely related with body mass index and insulinvalues. It is postulated to play an important role in hyperphagia. Direct quote from Pediatric endocrinology... 'fasting ghrelin levels were obtained in children with Prader Willi syndromeand found to be elevated 3-4 times when compared to children who are obese'. Pancreatic polypeptide Y (PYY) is normally secreted from endocrine cells of the ileum and colon. It reduces energy and its reduced levels in the patients of Prader Willi syndrome may contribute to hyperphagia and obesity
Which one of the following is an autosomal dominantdisorder: (a) Duchenn's muscular dystrophy (b) Fragile X syndrome (c) Fanconi's anemia (d) Huntington's chorea
Huntington's chorea
Which of the following disorders has been shown to begenetically transmitted by single autosomal dominantgenes? (a) Catatonic schizophrenia (b) Phenylketonuria (c) Creutzfeldt-Jakob's disease (d) Huntington's disease
Huntington's disease
If a chromosome divides in an axis perpendicular tousual axis of division it is going to form:
Isochromosome Isochromosome formation results when one arm of a chromosome is lost and the remaining arm is duplicated, resulting ina chromosome consisting of two short arms only or of two long arms.• An isochromosome has morphologically identical genetic information in both arms.• The most common isochromosome present in live births involves the long arm of the X.• The Xq isochromosome is associated with monosomy for genes on the short arm of X and with trisomy for genes onthe long arm of X.• The reason for the formation of an isochrome is the centromere misdivision. Instead of dividing longitudinally toseparate the two sister chromatids, the centromere undergoes a transverse split that separated the two arms from oneanother...
Mitochondrial chromosomal abnormality leads to: (a) Leber's hereditary optic neuropathy (b) Angelman syndrome (c) Prader villi syndrome (d) Myotonic dystrophy
Leber's hereditary optic neuropathy Examples of mitochondrial inheritance are Leber's optic neuropathy, Leigh's disease, MELAS (mitochondrial encephalopathy, lactic acidosis and stroke like syndrome) NARP syndrome (Neuropathy, ataxia, and retinitis pigmentosa), KearnsSayre syndrome, Chronic progressive external ophthalmoplegia and Pearson syndrome.
The genetics involved in Down syndrome is:
Maternal non-disjunction Genetics of Down syndrome• Meiotic nondisjunction of chromosome 21 occuring in the ovum is seen in 95% cases with trisomy 21 and is the so,commonest cause of Down syndrome. The extra chromosome is of maternal origin.• There is a Strong relation with maternal age• It may also be seen with Robertsonian translocation and mosaicism.
True statements regarding the mitochondrial genesare: (a) Paternal transmission (b) Maternal transmission (c) Mendelian inheritance (d) Mitochondrial myopathy (e) Horizontal inheritance
Maternal transmission; (d) Mitochondrial myopathy: Human mitochondrial DNA (mt DNA)• Examples include- Leber's Hereditary Optic Neuropathy ,- Myoclonic Epilepsy with Ragged Red Fibers syndrome (MERRF), - Mitochondrial myopahty with Encephalopathy, Lactic Acidosis and Stroke (MELAS), - Autosomal dominant inherited mitochondrial myopathy with mitochondrial deletion (ADMIMY), - Kearns-Sayre syndrome ,- Chronic progressive external ophthalmoplegia, - Pearson syndrome and - Neurogenic muscular weakness with ataxia and retinitis pigmentosa (NARP)
Mitochondrial DNA is (a) Paternally inherited (b) Maternally inherited (c) Horizontal inheritance (d) Vertical inheritance (e) Mendelian inheritance
Maternally transmitted.
Karyotyping is done in which phase of cell cycle?
Metaphase Karyotyping is the study of chromosomes• Chromosomes are arrested in metaphase by ColchicineQ• These are then stained by many stains. Most commonly used stain is Giemsa stainQ, so called G-bandingQ• The chromosomes are arranged in order of decreasing lengthQ. Any alteration in number or structure of chromosomes can be easilydetected by karyotyping
A 16-year-old female Bholi presents to Dr. Sindhu,a gynecologist because she has never had menstrualbleeding. She is 132 cm tall, weighs 44 kg, has swellingaround the neck, increased carrying angle at the elbowand poorly developed secondary sexual characteristics.On performing a pelvic ultrasound, the physicianobserves her ovaries are small and elongated. Which ofthe following is the most likely cause of this patient'scondition? (a) Mitotic error in early development (b) Trinucleotide repeat expansion (c) Uniparental disomy (d) Balanced reciprocal translocation
Mitotic error in early development The patient described in the stem of the question appears to have Turner syndrome. The clinical manifestations of thiscondition are as follows
A 36-year-old retarded man with a strong history ofmental retardation among male relatives undergoesgenetic testing. His lymphocytes on metaphase arrestshow a breakpoint at q27.3 on the X chromosome. Thisman is at increased risk for which of the followingcardiovascular disorders? (a) Aortic stenosis (b) Atrial septal defect (c) Mitral valve prolapse (d) Tricuspid atresia
Mitral valve prolapse The patient in question is suffering from Fragile X Syndrome which is a familial form of mental retardation with featureslike lax skin and joints, flat feet, large ears, long narrow face with prominent jaw and nasal bridge and macro-orchidism. Mitral valve prolapse and aortic root dilatation are the serious complications of this disorder.• Aortic regurgitation related to aortic root dilatation and not stenosis (option a) is seen.• Common congenital cardiac malformations such as atrial septal defect (option b) or ventricular septal defect (option d) may be seenwith Down's syndrome and not Fragile X syndrome
8-year-old boy Gullu with the Down's syndrome hasan intelligence quotient (IQ) in the mid-normal range.Which of the following genetic mechanisms wouldmost likely account for the discrepancy between thechild's IQ and his appearance? (a) Balanced translocation (b) Chiasma (c) Mosaicism (d) Spermiogenesis
Mosaicism Mosaicism is the term used when cells with more than one type of genetic constitution are present in the same organism. The situation in the question uncommonly occurs when nondisjunction of chromosome 21 occurs during mitosis (ratherthan meiosis) in one of the early cell divisions. The degree to which the individual expresses the characteristics of thesyndrome depends on the number of cells involved and their distribution. Balanced translocation (choice A) does not produce features of any syndrome, because critical genetic material is not lost,although progeny may be affected when the translocated chromosome is added to a complement of otherwise normalchromosomes .Chiasma (choice B) refers to the "X"-shape of chromosomes undergoing exchange of genetic material in crossover. Spermiogenesis (choice D) refers to the development of sperm precursors into mature sperm.
An albino girl gets married to a normal boy, what arethe chances of their having an affected child and whatare the chances of their children being carriers? (a) None affected, all carriers (b) All normal (c) 50% carriers (d) 50% affected, 50% carriers
None affected, all carriers Albinism is an autosomal recessive (AR) disorder• AR disorders express only in homozygous state, i.e. if both alleles are mutant• If 'A' is normal allele and 'a' is mutant, then the given cross in the question can be made as Thus genotypically all offsprings are carriers and Phenotypically, all of then will be normal.
Trisomy 13 is identified as
Patau syndrome
Sickle cell disease is due to (a) Point mutation (b) Frame shift mutation (c) Nucleotide receptor blockage (d) Non sequence mutation
Point mutation
Majority of the human characteristics are determinedby multiple pairs of genes, many with alternate codes,accounting for some dissimilar forms that occur withcertain genetic disorders. What type of inheritanceinvolves multiple genes at different loci, with eachgene exerting a small additive effect in determining atrait? (a) Polygenic inheritance (b) Multifactorial inheritance (c) Monofactorial inheritance (d) Collaborative inheritance
Polygenic inheritance Polygenic inheritance involves multiple genes at different loci, with each gene exerting a small additive effect in determining a trait. Multifactorial inheritance is similar to polygenic inheritance in that multiple alleles at different loci affect theoutcome; the difference is that multifactorial inheritance includes environmental effects on the genes.
Maternal disomy of chromosome 15 is seen in :(a) Prader-Willi syndrome (b) Klinefelter's syndrome (c) Angelman syndrome (d) Turner's syndrome
Prader-Willi syndrome Prader Willi syndrome could be present because of the following: a. Deletion of paternal chromosome 15 or B .Uniparental disomy of maternal chromosome 15.
Chromosomal abnormality in Mongolism is
Trisomy 21
Barr body is not seen in: (a) Klinefelter syndrome (b) Turner syndrome (c) Normal female (d) XXX syndrome
Turner syndrome
Which of the following is an X-linked dominantdisorder? (a) Vitamin D resistant rickets (b) Familial hypercholesterolemia (c) Red green color blindness (d) Achondroplasia
Vitamin D resistant rickets
An 18 month old child Nonu is brought to a pediatrician.His mother noticed passage of altered color urine by himfor past 2-3 days. Laboratory examination revealed it tobe hematuria. Examination also reveals hypertensionand an abdominal mass. A tumor is localized to theright kidney and biopsy reveals a stroma containingsmooth and striated muscle, bone, cartilage, and fat,with areas of necrosis. The gene for this disorder hasbeen localized to which of the following chromosome
11 The diagnosis of this patient is Wilms' tumor. It occurs in children and typically presents with an abdominal mass as wellas with hypertension, hematuria, nausea and intestinal obstruction. Since it is derived from mesonephric mesoderm, it caninclude mesodermal derivatives such as bone, cartilage, and muscle. The Wilms' tumor suppressor gene (WT-1) has beenlocalized to chromosome 11 (11p). Other options• Chromosome 5 (option a) is the site of the tumor suppressor gene APC, which is involved in the pathogenesis of colon cancerand familial adenomatous polyposis.• Chromosome 13 (option c) is the site of the tumor suppressor gene for retinoblastoma and osteosarcoma (Rb) as well as theBRCA-2 gene for breast cancer.• Chromosome 17 (option d) is the site of p53 (involved in most human cancers), NF-1 (neurofibromatosis type I), and BRCA-1(breast and ovarian cancer).
The chances of having an unaffected baby, when bothparents have achondroplasia, are: (a) 0% (b) 25% (c) 50% (d) 100%
25% Achondroplasia is an autosomal dominant condition. Only one mutant allele is enough to cause disease. Thus, AA and Aa will be affected whereas aa will be unaffected. ['A' ismutant allele whereas 'a' is normal]. As is clear from the diagram, 3 out of 4, i.e. 75% of children will be affected and 1 out of 4, i.e. 25% children will be unaffected. However, please note that clinically the baby with AA genotype usually donot survive.
The approximate number of genes contained in thehuman genome is: (a) 40,000 (b) 30,000 (c) 80,000 (d) 1,00,000
30,000 genes Humans have a mere 30,000 genes rather than the 100,000 predicted only recently. Recent Robbins mentions the number of genes to 20,000 to 25,000. Genetics is the study of single or a few genes and their phenotypic effects. Genomics is the study of all the genes in the genome and their interactions. DNA microarray analysis of tumors is an excellent example of genomics in current clinical use. Epigenetics is heritable changes in gene expression that are not caused by alteration in DNA sequences.
The number of chromosomes in Turner syndrome is:
45 Turner syndrome is the most common cause of sex chromosomal abnormality in the females. It usually results from complete or partial monosomy of X chromosome and associated with hypogonadism in phenotypic females.Q Patients have the(45X) karyotype or may be mosaics.
A nineteen year old female with short stature, widespread nipples and primary amenorrhea most likelyhas a karyotype of: (a) 47, XX + 18 (b) 46, XXY (c) 47, XXY (d) 45 X
45X Given features (Female, primary amenorrhea, short stature, widely spaced nipples) suggests the diagnosis of Turner's syndrome. Turner's Syndrome Turner's syndrome is the most common sex chromosomal disorder in phenotypic females. Turner's syndrome results from complete or partial loss of one X chromosome (45, XO) and is characterized by hypogonadism inphenotypic females
Males who are sexually underdeveloped withrudimentary testes and prostate glands, sparse pubicand facial hair, long arms and legs and large hands andfeet are likely to have the chromosome complement of :(a) 45, XYY (b) 46, XY (c) 46, XXY (d) 46, X
46, XXY It is a typical case of Klinefelter syndrome. The features pointing towards this diagnosis are:• Male phenotype• Hypogonadism [rudimentary testes]• Decreased secondary sexual characteristics [sparse pubic and facial hairs]• Disproportionately long arms and legs. Patients with Klinefelter syndrome have extra X chromosome, so they may be 47,XXY or 46XY/47 XXY mosaics.
The number of chromosomes in Klinefelter syndromeis:
47 Klinefelter syndrome is the most common chromosomal disorder of males associated with hypogonadism and infertility. It is due toextra-X-chromosome. Classically, it is 47, XXY. Other variants can have 48 XXXY, rarely 49 XXXY or mosaics can be therewith some cells containing normal 46, XY and others 47, XXY.
tall man with gynecomastia and testicular atrophyhas a testicular biopsy that shows sparse, completelyhyalinized seminiferous tubules with a completeabsence of germ cells and only rare Sertoli cells. Leydigcells are present in large clumps between the hyalinizedtubules. Which of the following genetic disordersshould be suspected? (a) Testicular feminization syndrome (b) Trisomy 18 (c) Trisomy 21 (d) 47, XXY
47, XXY The testicular changes described are those observed in Klinefelter's syndrome, most often due to 47, XXY genetics.• Testicular feminization syndrome (choice A) is due to a genetically determined unresponsiveness to testosterone that produces aphenotypic female in an individual with 46, XY chromosomes.• Trisomy 18 (choice B) is Edwards' syndrome, characterized by facial features that are small and delicate.• Trisomy 21 (choice C) is the most common trisomy, Down syndrome.
The classic karyotype of Klinefelter's syndrome is:
47XXY
Resolution provided by the various FISH techniques interphase nuclei
50- 1000 kb
