39 public questions tagged with this topic.
Hemophilia is a sex-linked recessive disorder caused by a mutation in the X chromosome. This follows from NCERT principle where relation explains outcome clearly for students.
Ref: NCERT Biology Textbook for Class XI and XII (Botany section), Chapter: Biology - Botany portion covering relevant concept, Topic: Plant structure, physiology and applications.
Mutations in PAX6 transcription factor cause aniridia, congenital absence or severe hypoplasia of iris, accompanied by corneal opacification, cataracts, foveal hypoplasia, and nystagmus. Pax6 continues expression in iris, cornea, retina throughout development maintaining ocular progenitor gene networks. Dominant haploinsufficiency reduces DNA binding to target promoters. Cataract alone typically results from crystallin mutations, retinal detachment from other causes, myopia polygenic. Aniridia represents classic dosage-sensitive phenotype of PAX6 linked to 11p13 deletion, demonstrating pleiotropic eye regulatory role beyond lens induction and corneal maintenance.
Ref: NCBI Bookshelf, Molecular Biology of Eye: PAX6 mutations causing aniridia and ocular anomalies.
ACA establishes positive feedback loop of cAMP signaling that organizes collective movement. Mutants lacking functional ACA fail to synthesize pulses, therefore no extracellular cAMP wave propagates, cells do not polarize, stream, or form mounds, and developmental program arrests early. Intracellular cAMP remains low, preventing induction of early genes like discoidin and contact site A. Phenotype includes lack of aggregation territory, no slug formation despite starvation. Normal aggregation patterns require ACA-mediated relay; excessive aggregation would require increased cyclase activity, while normal culmination occurs only if aggregation succeeded, demonstrating ACA indispensability at initiation of multicellular development.
Ref: Science, ACA null phenotype - failure to aggregate, cAMP pulse rescue and developmental arrest.
Adenosine deaminase deficiency autosomal recessive SCID became earliest successful gene therapy target due biological features favoring correction. Enzyme chromosome 20q13.12 deaminates adenosine to inosine and deoxyadenosine to deoxyinosine, deficiency leads accumulation deoxyadenosine converted deoxycytidine kinase to dATP elevated dATP allosterically inhibits ribonucleotide reductase essential dNTP synthesis DNA replication lymphocyte clonal expansion triggers apoptosis intrinsic pathway resulting absent T B NK cells. Lymphoid lineage provides selective advantage because corrected cells detoxify metabolite locally via metabolic cross-correction proliferate growth advantage while uncorrected die amplifying gene-marked population without myeloablation similar natural reversion mosaicism. HSC accessible bone marrow aspiration amenable retroviral transduction MoMLV vector carrying ADA cDNA under LTR promoter. First trial 1990 Anderson Blaese Rosenberg infused autologous transduced T lymphocytes demonstrating persistence partial enzyme activity. Later Strimvelis product autologous CD34 cells gamma retroviral vector achieved immune reconstitution and became first ex vivo gene therapy approved Europe highlighting importance long-term monitoring leukemia due insertional activation.
Ref: Lancet ADA First Gene Therapy NEJM 1990; NCBI SCID Gene Therapy History; NCERT Biotechnology Applications ADA Chapter 12.
Gene augmentation alias addition therapy provides supplemental functional copy gene compensating recessive loss-of-function mutation where endogenous loci produce truncated or misfolded protein rapidly degraded proteasome or nonsense-mediated decay. Delivered cDNA lacks introns and native regulatory elements codon-optimized enhancing translation and CpG depleted reducing TLR9 activation expressed under heterologous constitutive promoter chicken beta-actin with CMV enhancer or tissue-specific transthyretin promoter driving strong transcription independent defective locus that remains present but inactive. After nuclear entry via nuclear pore, construct episomally or integrally transcribed RNA polymerase II mRNA capping polyadenylation SV40 late signal export NXF1 pathway translation rough ER producing protein folding via BiP disulfide isomerases trafficking Golgi acquiring glycans secreted plasma restoring metabolic pathway such as phenylalanine hydroxylase or clotting factor activity above 5 percent threshold converting severe to mild phenotype. Strategy avoids chromosome editing avoiding double-strand break off-target risks while achieving therapeutic threshold suitable dose control. This mechanistic insight guides vector optimization, dosing strategies, and clinical safety monitoring essential for translational development and regulatory evaluation.
Ref: NIH Gene Augmentation Therapy Strategy; Watson Molecular Biology Gene Augmentation Chap 15; NCBI Bookshelf Gene Addition https://www.ncbi.nlm.nih.gov/books/NBK21981/.
Lysosomal storage disorders form a group of about seventy rare inherited metabolic diseases sharing unifying pathophysiology despite diverse enzyme defects. Mutations in genes encoding lysosomal acid hydrolases, accessory activator proteins GM2 activator and saposins, sulfatases requiring formylglycine modification by SUMF1, or lysosomal integral membrane transporters such as cystinosin and sialin impair specific catabolic steps. Because residual enzyme activity falls below threshold, typically less than ten percent of normal, undegraded macromolecular substrates such as sphingolipids, mucopolysaccharides, glycogen, oligosaccharides, ceroid lipofuscin or free amino acids accumulate inside endolysosomal compartments, physically swelling lysosomes to microns, engorging cytoplasm, disrupting trafficking, autophagy, mTOR signaling and calcium homeostasis via TRPML1 inhibition. Neurons, macrophages, hepatocytes and skeletal muscle heavily loaded with storage material display vacuolation, impaired function and apoptosis. Examples include Tay-Sachs with GM2 ganglioside accumulation from hexosaminidase A deficiency, Gaucher with glucosylceramide, Pompe with glycogen, and cystinosis with cystine crystals due to defective cystine exporter. Cells show material overload rather than overexpression of enzymes; often mutant enzymes are unstable, misfolded and degraded by ER-associated degradation. Lysosomal biogenesis via TFEB compensates initially but fails as storage progresses, causing multi-systemic pathology often beginning in infancy.
Ref: Parenti et al., Nature Reviews Drug Discovery 2015: Lysosomal Storage Disorders – Substrate Accumulation.
PCR (Polymerase Chain Reaction) is used to amplify DNA, making it possible to detect genetic disorders_x000D_ early.
Ref: NCERT Class 12 Biology Chapter 10: Biotechnology and its Applications Medical Applications - Molecular Diagnosis - PCR ELISA
PCR (Polymerase Chain Reaction) is used for early detection of genetic disorders by amplifying specific_x000D_ DNA sequences.
Ref: NCERT Class 12 Biology Chapter 10: Biotechnology and its Applications Medical Applications - Molecular Diagnosis - PCR ELISA
Gene therapy involves correcting genetic defects by introducing functional genes into cells.
Ref: NCERT Class 12 Biology Chapter 10: Biotechnology and its Applications Medical Applications - Gene Therapy - ADA SCID
Gene therapy is a technique used to replace defective genes with functional ones to treat genetic_x000D_ disorders.
Ref: NCERT Class 12 Biology Chapter 10: Biotechnology and its Applications Medical Applications - Gene Therapy - ADA SCID
Gene therapy is not limited to bacterial infections; it is primarily used to treat genetic disorders by_x000D_ correcting defective genes.
Ref: NCERT Class 12 Biology Chapter 10: Biotechnology and its Applications Medical Applications - Gene Therapy - ADA SCID
Gene therapy is used to treat adenosine deaminase (ADA) deficiency by inserting a functional ADA gene.
Ref: NCERT Class 12 Biology Chapter 10: Biotechnology and its Applications Medical Applications - Gene Therapy - ADA SCID
