DNA, Chromosomes & Human Genome PDF

DNA, CHROMOSOMES & HUMAN GENOME DR. EMAN RAMADAN ABD EL-HAMID LECTURER OF MEDICAL GENETICS FOMSCU  ILOs Definitions What is the genetic material? DNA DNA packaging Chromosomes Human genome (Nuclear & Mitochondrial) Definitions GENETICS: The branch...

DNA, CHROMOSOMES & HUMAN GENOME DR. EMAN RAMADAN ABD EL-HAMID LECTURER OF MEDICAL GENETICS FOMSCU  ILOs Definitions What is the genetic material? DNA DNA packaging Chromosomes Human genome (Nuclear & Mitochondrial) Definitions GENETICS: The branch of biology concerned with the study of the origin, transmission, and expression of genetic information. Medical Genetics: The branch of medicine concerned with the inheritance, diagnosis and treatment of diseases with genetic background. Molecular Genetics: The study of the structure and function of genes at the molecular level. Cytogenetics: The study of chromosomes, their structure, and their inheritance. WHAT IS THE GENETIC MATERIAL? WHAT IS THE GENETIC MATERIAL? Chromosome WHAT IS THE GENETIC MATERIAL? Chromosome WHAT IS THE GENETIC MATERIAL? DNA DNA DNA DNA Nucleotide DNA Pentose Penta-: 5 Deoxy-Ribose Sugar ‘ Prime DNA Nitrogenous Bases Nitrogenous base is attached to 1’ carbon of deoxyribose sugar. T A C G DNA Phosphate group is attached to 5’ carbon of deoxyribose sugar. DNA Sugar-Phosphate Backbone (Phosphodiester Bonds) Phosphodiester bond (Covalent bond) (Between 3’ carbon of deoxyribose sugar of one nucleotide and an oxygen atom of phosphate at 5’ carbon of the adjacent nucleotide). A DNA strand has: 5’ end: with a free phosphate group 3’ end: with a free hydroxyl (OH) group DNA Hydrogen Bonds Guanine is paired with cytosine by three hydrogen bonds. Adenine is paired with thymine by two hydrogen bonds. COMPLEMENTARETY DNA Complementary Anti-parallel Anti-parallel Anti-: against, opposite of DNA Deoxyribonucleic acid Polymer Poly-: many The primary carrier of genetic information. -mer: part A polymer of nucleotides, in which the sugar residues are deoxyribose, and the bases are cytosine, guanine, adenine and thymine. consisting of two long chains (strands) twisted into a double helix and joined by hydrogen bonds. 1-bp 4-bp 1-bp Base pair (bp) 1-bp Kilobase pair (kb) = 1000-bp 1-bp DNA PACKAGING DNA PACKAGING DNA is associated with proteins and is coiled to form chromatin. Nucleosome Looped DNA Solenoid Chromatid filament domains DNA PACKAGING 1. Nucleosomes ▪ DNA (~140-bp long) wraps ~1.75 times around a core of histone proteins. ▪ The core consists of 2 molecules of each of the histone proteins → H2A, H2B, H3, and H4 (octamer) ▪ Linker DNA: The DNA between the nucleosomes, H1 histone interacts with the linker DNA. DNA PACKAGING 1. Nucleosomes Nucleosome Filament (11 nm) “Beads on a string” DNA PACKAGING 2. Solenoid The nucleosome filament is coiled into a helix with 6 nucleosomes per turn (chromatin fibers). Chromatin fiber (30 nm) DNA PACKAGING 3. Looped Domains Loops of chromatin fibers bind to non-histone scaffold proteins. Looped Domains (loops) (70 nm) DNA PACKAGING 4. Chromatid The looped domains are further compacted to form the chromatid.  1 Nucleosome Filament 2 Solenoid 3 Looped Domains 4 Chromatid  Packing Level Thickness Ratio DNA 2 nm Nucleosome filament 1 11 nm 6-7 (Beads on a string) 2 Solenoid (Chromatin fiber) 30 nm ~40 Loops 3 70 nm ~700 (Looped domains) 4 Chromatid 700 nm ~10,000 MITOTIC CHROMOSOME 1400 nm CHROMOSOMES Chromosomes are rod-shaped structures within the nucleus that contain DNA. Each chr. consists of one double- stranded DNA molecule complexed with protein. Can be seen under the microscope only in dividing cells. CHROMOSOMES Diploid organism: e.g., Human ▪ Human somatic cell has 46 chromosomes, grouped in pairs (23), one inherits one copy from one of the parents. ▪ First 22 pairs called autosomes and identical in both sexes. ▪ The 23rd pair called sex chromosome is different in both sexes Karyotype: Number and appearance of chromosomes in the nucleus of a eukaryotic cell. CHROMOSOMES Somatic cells: 46 chromosomes (23 pairs of chromosomes) 22 pairs of autosomes + 1 pair of sex chromosomes Female: two X chromosomes Male: one X and one Y chromosome CHROMOSOMES Gametes (Ova, Sperm): 23 chromosomes 22 autosomes + 1 sex chromosome (Ova , X Chr. (Sperm, X or Y Chr.) CHROMOSOMES Homologous chromosomes (homologues) ▪ Members of a pair of chromosomes Carry matching genetic information ▪ One member is inherited from the father (paternal), the other from the mother (maternal). Telomere Centromere Telomere CHROMOSOMES Identification CHROMOSOMES 1. Identification according to size: ▪ Chromosome pairs are numbered from 1 to 22 from the longest to the shortest. ▪ Exception: chromosome 22 is longer than chromosome 21 CHROMOSOMES 2. Identification according to centromere position: Metacentric Submetacentric Acrocentric Metacentric Acrocentric Submetacentric CHROMOSOMES 3. Identification according to banding pattern: ▪ Chromosome stains produce a series of light and dark bands. ▪ These bands are unique and specific to each chromosome. GENERAL ORGANIZATION OF HUMAN GENOME Human genome: is the whole population of genes. NUCLEAR GENOME Shape: Linear Double stranded DNA Size: 3.1 Gb (3100 Mb) 99% of cell DNA Site: Distributed between different 46 chromosomes (44 autosomes + 2 sex chromosomes) in nucleus. Number of genes: 20.000 - 40.000 Distribution: varies, gene rich chromosomes (19 & 22), gene poor chromosomes (4 &18)  Nuclear Genome 50% 50% Single-copy DNA Repetitive DNA sequences sequences Genes & Dispersed Non-gene Tandem gene related repetitive sequences repeat DNA sequences DNA Single - copy DNA (Unique DNA): DNA sequence that represented only once per haploid genome. 1- Genes & gene related elements Protein-Coding sequences (1.5% of genome) + gene regulatory elements (5% of genome) 2- Non-gene sequences Unknown function Found in short stretches (several Kbs) interspersed with repetitive DNA Repetitive DNA sequences: DNA nucleotide sequences repeated hundreds or millions of times in the genome. Function: ✓Maintain chromosome structure. ✓Important source of variation between different individuals. 1- Tandem repeat DNA. 2- Dispersed repetitive DNA. 1- Tandem repeat DNA (Satellite) ▪ Short nucleotide repeats. ▪ Clustered in one or more location along the chromosome. ▪ 10-15% of the repetitive sequences of the genome.  Tandem repeat DNA ( Satellite) Micro-Satellite DNA, Short tandem repeats (STRs), Simple sequence repeats (SSRs) Mini-Satellite DNA, Variable number tandem repeats (VNTRs) (Used in DNA fingerprinting) 2- Dispersed repetitive DNA ✓Short interspersed nuclear elements (SINEs) ✓Long interspersed nuclear elements (LINEs)  Mitochondrial genome Shape: Circular Double stranded DNA Size: 16 Kb in size (less than 0.03% of length of the smallest nuclear chromosome) Number & Distribution : Most cells have 100-1000 copies of mtDNA except ovum has about 100.000 copy.  Mitochondrial genome Mitochondrial DNA (mtDNA): ▪ Formed of 2 strands: Heavy strand (H): rich in G Light strand (L): rich in C ▪ Contains 37 genes encoding 13 polypeptides, 22 tRNAs, and 2 rRNAs (16s rRNA &12s rRNA). ▪ Not packaged into chromatin. ▪ very little repetitive DNA  Mitochondrial genome Mitochondrial DNA (mtDNA): ▪ Function: Produce enzymes required for oxidative phosphorylation and electron transport ▪ Inheritance: Non-mendelian inheritance (Exclusively maternal inheritance) but new researches still emerging on evidence paternal role SUGGESTED READING Books Medical Genetics (Ed. Jorde, Carey, Bamshad) Thompson & Thompson Genetics in Medicine Emery’s Elements of Medical Genetics