The document discusses genetics and genetic disorders. It provides background on chromosomes, genes, Gregor Mendel's foundational work in genetics, DNA structure, mRNA, tRNA, amino acids, and the genetic code. It also covers topics like genetic engineering, gene therapy, and molecular techniques used to study human diseases.

2. GENETIC DISORDERS (Introduction) Dr. Shahab Riaz

4. Chromosome: Greek ( chroma , color) and ( soma , body) bcz strongly stained by particular dyes organized structure of DNA and protein , found in cells single piece of coiled DNA containing many genes , regulatory elements and other nucleotide sequences In eukaryotes, nuclear chromosomes are packaged by proteins into a condensed structure called chromatin very long DNA molecules to fit into the cell nucleus

6. Gene: basic unit of heredity in a living organism information to build and maintain the cells and pass genetic traits to offsprings In general terms, a gene is a segment of nucleic acid that, taken as a whole, specifies a trait

8. Gregor Mendel

9. History: Gregor Mendel (1822–1884) a priest and scientist In 1860s, studied inheritance in pea plants father of genetics for his study of the inheritance of certain traits in pea plants hypothesized a factor that conveys traits from parent to offspring over 10 years of his life on one experiment showed that the inheritance of these traits follows particular laws Mendel's work was not recognized until the turn of the 20th century Didn’t use the term gene , explained results in terms of inherited characteristics dominant and recessive traits, the distinction between a heterozygote and homozygote , genotype and phenotype

10. Deoxyribonucleic acid (DNA): nucleic acid genetic instructions & the long-term storage of information blueprints , or a code for development and functioning Construction of cellular proteins and RNA molecules DNA segments that carry this genetic information are called genes

11. DNA Structure: two long polymers of simple units called nucleotides backbones made of sugars and phosphate groups joined by ester bonds two strands are anti-parallel Attached to each sugar is one of four types of molecules called bases sequence of these four bases along the backbone that encodes information

15. Messenger ribonucleic acid (mRNA) : molecule of RNA encoding a chemical "blueprint" for a protein product mRNA is transcribed from a DNA template carries coding information to the sites of protein synthesis : the ” ribosomes ” on RER the nucleic acid polymer is translated into a polymer of amino acids : a “ protein” In mRNA as in DNA, sequence of nucleotides arranged into codons consisting of three bases each Each codon encodes for a specific amino acid stop codons terminate protein synthesis

16. Codon: Base triplet in mRNA transcribed by DNA If the base triplet in the DNA sequence is GCT Then corresponding codon on the mRNA strand will be CGA Transfer RNA (tRNA): mediates recognition of the codon provides the corresponding amino acid Ribosomal RNA (rRNA): central component of the ribosome's protein manufacturing machinery Anti-Codon: sequence of three adjacent nucleotides in transfer RNA binds to a corresponding codon in messenger RNA designates a specific amino acid during protein synthesis

19. 20 Amino Acids In Human Protein: Table of DNA Base Triplets, RNA Codons & Anticodons

20. GENETICS: Ancient Greek genetikos , “genitive” and that from genesis , “origin” science of heredity and variation in living organisms living things inherit traits from their parents  prehistoric times  improve crop plants and animals through selective breeding Modern genetics basis by Gregor Mendel

21. Genome: full set of chromosomes or genes in a gamete So a regular somatic cell contains two full sets of genomes In haploid organisms , including bacteria , viruses , and mitochondria , a cell contains only a single set of the genome Genomics: study of the genomes of organisms entire DNA sequence of organisms and fine-scale genetic mapping efforts Research of single genes does not fall into the definition of genomics

22. Importance of Genetics Life time frequency  670/1000 Classic genetic diseases + CVS diseases and cancer Some diseases have both environmental + genetic role (atherosclerosis / HTN) In medical practice  Iceberg of Genetic diseases  less severe 50% of spontaneous abortions  gross chromosomal abnormalities

23. Importance of Genetics 100,000 previously thought but actually approx 30,000 Different combinations  > 100,000 proteins Fully formed proteins can be sliced/stitched  > peptides than expected Avoiding intra-uterine diseases Thalassemia  inter-marriages Treatments of cancer  Genetic Level

24. Interesting Fact 99.9% of genomic DNA sequence of any two humans is the same 0.1% rest of the genome  accounts for the differences in features  approx. 3 million base pairs

25. Genetic Advancements

26. Molecular Basis of Human Diseases Two general strategies used to isolate involved genes Functional Cloning or Classical Approach: Abnormal gene product / protein known Isolate normal gene and clone Determine molecular changes causing the disorder Positional Cloning or Candidate Gene Approach: In some diseases, multiple genes involved or no clue of defective product Ignores the phenotype or protein product Instead mapping disease phenotype to specific chromosome location Marker genes identified  Close proximity to disease locus Localized narrow limits  clone DNA from relevant site in vitro Identification of protein  aberrant protein encoded by mutant genes

28. Genetic Engineering Production of human biologically active agents Recombinant DNA technology Improving crop technology manufacture of synthetic human insulin through the use of modified bacteria manufacture of erythropoietin in hamster ovary cells Growth hormone GM-CSF & G-CSF

29. Genetic Engineering Isolation of the genes of interest Insertion of the genes into a transfer vector Transfer of the vector to the organism to be modified Transformation of the cells of the organism 5. Selection of the genetically modified organism (GMO) from those that have not been successfully modified

31. Gene Therapy insertion of genes into an individual's cells and tissues to treat a disease hereditary disease in which a deleterious mutant allele is replaced with a functional one Although the technology is still in its infancy, it has been used with some success. Appropriate Vectors ??? Random Insertion in other Cells