Human Karyotype and Pseudoautosomal Regions

Human Karyotype

• Somatic cells are diploid, possessing 46 chromosomes (2n).
• Germ cells are haploid, containing 23 chromosomes (1n).
• The sex chromosome determines the sex and sex-linked characteristics of an organism.
• Humans have two sex chromosomes: X and Y.
• Each diploid cell has two sex chromosomes: females have XX, and males have XY.
• Chromosomes that aren't sex chromosomes are called autosomes, which are the same for all.

Pseudoautosomal Regions (PARs)

• PAR1 and PAR2 are short homologous regions on the X and Y chromosomes.

• PAR behaves as an autosome by recombining during meiosis.

• Female somatic cells have 46 chromosomes (2n), with an XX makeup and germ cells have 23 chromosomes (1n), with an X.

• One X chromosome in all somatic cells of females becomes inactive, forming a Barr body.

• Barr bodies can be identified by specific staining methods in the interphase nucleus.

• Male somatic cells have 46 chromosomes (2n), XY and their germ cells have 23 chromosomes (1n), an X or a Y.

• Their X chromosome remains active and does not form a Barr body.

Chromosome Groups and Characteristics

• Group A (chromosomes 1-3) consists of large metacentric chromosomes.
• Group B (chromosomes 2, 4-5) consists of large submetacentric chromosomes.
• Group C (chromosomes 6-12, X) consists of medium-sized metacentric or submetacentric chromosomes.
• Group D (chromosomes 13-15) consists of medium-sized acrocentric chromosomes with satellites.
• Group E (chromosomes 16-18) consists of relatively short metacentric and submetacentric chromosomes.
• Group F (chromosomes 19-20) consists of short metacentric chromosomes.
• Group G (chromosomes 21-22, Y) consists of short acrocentric chromosomes with satellites.
• The Y chromosome has no satellites.

The Nucleolus

• The site of ribosomal RNA (rRNA) transcription, pre-rRNA processing, and ribosome subunit assembly.
• The nucleolus is not membrane-bounded.
• Under a light microscope, interphase cells show a round formation in the nucleus with distinct structure.
• Fibrillar centers contain rRNA genes with RNA synthesis enzymes (transcription).
• The dense fibrillar component contains protein-bounded rRNA molecules involved in pre-rRNA processing.
• The granular component contains pre-ribosomal particles for ribosome subunit assembly.

Prokaryotic Chromosomes and Nucleoid

• The nucleoid is a complex of DNA and RNA molecules with nucleoproteins, not enclosed by a membrane.
• Prokaryotic DNA is circular, not attached to histone proteins, and usually consists of one circular molecule, though a few molecules are possible.
• Plasmids are small, circular molecules containing genetic information that contributes to the sensitivity to toxic substances. They play a role in genetic recombination.
• Stretched DNA in E. coli is about 1400 µm long, while the cell itself is only 1 to 5 µm.
• The nucleoid is composed of DNA associated with DNA-binding proteins that help maintain its structure.

Supercoiling in Prokaryotic Chromosomes

• DNA gyrase introduces supercoils, while DNA topoisomerase I prevents excessive supercoiling.
• Topoisomerase gene expression, the ATP to ADP concentration ratio, and transcription can influence supercoiling.

Mitochondrial Chromosome

• The mitochondrial chromosome is a self-replicating organelle and is thought to have originated from a purple bacteria.
• Mitochondria's essential genes have been transferred to the nuclear chromosomes.
• The outer membrane is composed of phospholipids and proteins, and is permeable to nutrient molecules, ions, ATP, and ADP via porins.
• The inner membrane is folded into cristae, increasing the surface area for chemical reactions like ATP production.
• The inner membrane is only permeable to oxygen and ATP via regulated metabolite transfer.
• The intermembrane space is similar to the cytosol.
• The matrix is a mix of proteins and enzymes necessary for synthesizing ATP molecules, mitochondrial ribosomes, tRNAs, and mitochondrial DNA (mtDNA).
• MtDNA is circular, negatively supercoiled, and located in the matrix, typically containing 4 to 10 copies.
• Top1mt, Top3a, and Top2ß have been found in mitochondria, encoded in the nuclear genome.
• Mitochondria are self-replicating, transmit cytoplasmic inheritance, and produce aerobic ATP, and are 13x more efficient than the anaerobic version.
• They maintain ion homeostasis, store calcium ions, synthesize steroids, and contain pro-apoptotic molecules.

The Genetic Code

• The genetic code comprises DNA or RNA sequences that determine amino acid sequences for protein synthesis and functions as the basis of heredity.
• 64 codons (triplets) correspond to the 20 amino acids used for protein synthesis, along with start and stop signals. The code is non-overlapping.
• AUG is the start codon; for methionine but UAA, UAG, and UGA are stop codons, but instead encode Selenocysteine (Sec).

Genetic Code in Mitochondria

• Mitochondrial genetic code is slightly different from the standard genetic code.
• UGA codon encodes for tryptophan (Trp), unlike encoding for Stop.
• AGA and AGG codons encode for Stop, unlike encoding for arginine (Arg).
• AUA and AUU codons encode for methionine (Met) and isoleucine (Ile).
• CUU, CUC, CUA, and CUG codons encode for leucine (Leu), unlike encoding for threonine (Thr).

The Gene

• The gene contains chromosomal DNA sequence needed for synthesizing a functional protein or RNA molecule. It is the fundamental unit of heredity.
• The gene includes coding regions (exons), introns, and transcription-control regions.
• The majority of genes encode proteins, but other encode tRNAs, rRNAs, and other types of RNA.
• At the 5` end of the gene, it includes a promoter region, which contains sequences required for transcription initiation.

The gene

• The 5`-region contains DNA elements like the TATA box, CpG island, and locus control region which determines transcription of different genes.
• TATA box located 25 to 30 bp upstream that is crucial for determining where transcription starts.
• 24% of human genes have this regulatory sequence, mostly found in tissue-specific genes while it isn't in common "housekeeping" genes.

Gene components.

• CpG islands are sequences rich in C and G that are found in many genes including housekeeping, tissue-specific, and developmental regulator genes.
• They contain a CG-rich stretch of 20–50 nucleotides within ~100 base pairs upstream of the start-site region.
• Some transcription factors bind to these islands, but are targeted for DNA methylation which can repress gene expression.

Gene components.

• 5`UTR (untranslated region) contains a initiator codon (initiator sequence, Inr), which have a cytosine (C) at the-1 position and an adenine (A).
• The sequences promote ribosome binding with mRNA.
• "Open reading frame" (ORF) starts at the start codon and stop to stop codon.
• The first codon on the coding strand of DNA is ATG, whereas the strand's last codon will be a STOP codon such as TAG; TAA; TGA.

More gene components

• The 3`UTR contains regulatory sequences to promote rapid mRNA degradation and regulate translation levels.
• Polyadenylation [poly(A)] signals (PAS) are in eukaryotic protein-coding.
• A central AAUAAA motif is a 3'-end cleavage signal that promotes downstream transcriptional termination.
• Control of gene activity in eukaryotic cells relies on balance of activators and repressors.
• Enhancers are regulatory DNA sequences that binds to transcription factors, which enhances transcription.
• Silencers are bound by repressors and prevents regulatory silencer sequences, and turns of transcription.

Locus Control Region and Genome

• The locus control region (LCR) enhances of the expression of linked genes in globin-coding genes.
• Protein coding genes has solitary genes of copy one that also has duplicated genes with close, non-identical sequences located within 5–50 kb of one another.
• Nonfunctional pseudogene copies which contains exons of a functional genes, that encode rRNA's.
• The constitutive (housekeeping) genes are for cellular functions, is relatively constant, not influenced by environmental factors, and has simpler regions without TATA box.
• Facultative genes have inducible expression, like CpG island, and are tissue based.

The Genome

• The genome is a total set of genetic content contained in a haploid set of chromosomes in eukaryotes but its also a single strand DNA in virus.
• The Eukaryotic has human genome in the nucleus but also through mitochondrial genome.
• Protein coding genes count for less of the genome, which leads to the highly conserved sequences and more.
• More complex organisms have decreased gene density (eukaryotes vs. prokaryotes).
• Regions of the genome with similar characteristics or organization, replication, and expression are not arranged randomly but, rather, tend to be clustered together.

Intergenic Regions

• Repetitious DNA includes Satellite, microsatellite and minisatellite DNA
• Satellite DNA associated with heterochromatin and vary in length.
• Minisatellites includes telomeres or subtelomeres.
• Microsatellites are DNA- dispersed which is throughout all chromosomes, 1–4 bp long, that's mostly found through regulatory sequences.
• Transposones are transposable mobile DNA elements move and migrate.
• Retrotransposones are a copied mechanism the reverse transcriptase turns the retrotransposon into DNA and puts into location.
• LINEs (Long interspersed nuclear elements can cause mutations during the retrotransposition.
• Aprox 80% of human have LINE-1 that's 100-400 bp, but Retrovirus-like elements has LTR.

Mitochondrial Genome

• Mobile elements can transpose or move DNA, and can be an increase in the copy number of a transposon during the cell cycle.
• Unique DNA sequences are non-coded, and important genome's promote promote certain recombination, inversion, and duplication, and effect long term evolution
• The circular double stranded DNA has 16.6 kilobases (kb) in length and include 37 gene
• There are 28 genes in one strand, with 9 in the other that contain tRNAs.

Prokaryotic genome

• Made up of structure that doesn't contain the introns, promoters, or regulatory sequence.
• Doesn't really go through the same steps as Eukaryotic genomes.
• Has few transposbale Squence but has IS insertion sequence
• The operons have many cells and genes regulated.

Lac operon in E Coli

• Functions to produce Enzyme to break down milk.
• Then when Milk is present, it turn on and the enzymes produce
• 2 copies of genes and 3 Functional sequences.
• The Promoter(P) is needed for Rna, the enzyme that performs and the Operator is Regulatory Bounded for more protein/

Changes in genome leading to pathology

• Ex: Fragile X Syndrome causes a result through autosomal disorder
• Has tandem that repeats and manifest through male.

Gene Expression

• Gene expression can is like translation in the genome sequence
• This requires to steps, transcription and translation process.

Transcription and Translation

• Transcription is mainly where generic information stored in a DNA strand into Messenger RNA with help of RNA.
• The Translation is a step and sequence of proteins to produce a chain.
• The Initiation starts for the cluster assembles, it end a cluster of proteins assembles with sequences.
• During Imitation process, RNA polymerase form a type of transcription within and and starts the polymerization.

RNA Polymerases

• RNA polymerase II initiate's genes while RNA polymerase I initiate's a rRNA encoding.
• RNA is made from two ribonucleotides (rNTPs), with help of phosphodiesters.
• Elongation happens on both sides.
• Transcriptions is created 5.3 direction.

RNA Processing

• The the protein transcripts is referred to as pre-mRNA to form a functional mRNA.
• When the RNA grows, the chain immediately makes it synth 5. caps.
• A cap protect the process if mRNA is from Enzymatic degradation and goes to cytoplasm.
• If there is an the end it uses and endonuclease to provide a 30H group.

Post-transcriptional mechanism

• The processing mainly goes to ribosomes and mRNA goes to the cytoplasm
• Goes through cytoplasm and translation at the same tie
• Eukaryotic structure has a 3 RNA polymerases as prokaryotes just has one.
• Eukaryotic structure has more mRNA then prokaryotic.

Inhibitors.

• Inhibitors main function is to regulate inhibitors and is called a- Amantin.

Ribosomes

• The ribosome structure is protein in the cells that elongate a polypeptide to amino acids in the molecule's sequences.
• The cells each have a larger and smaller sequence.

RNA

• RNA transfers and detects more.
• The molecules contain sequence and anticodon to parter with.

Transcription initiation

• The translation is bounded by a ribosomal that bind the subunit and mRNA that help the cell start sequence.

Steps of Translation

• A specific Trna goes to to a specific codon, this binding is the ribosomal structure
• The complex is made to help help with the protein sequences
• After Elongation, amino is added by the protein the ribosome in the sequence.

Steps of Transcription

• The codons is a signal to give of its genetic information. It completes the mRNA info within the gene and poly peptide. The translation is prokaryotes and Eukaryotes.

How do translation with prokaryotes dofferentiate form eukaryotes?

• In prokaryotes : the cytoplasm is in the Cytoplasm and the first amino acid is the first activated Met sequences.
• Also requires 3 phases of releasing factors and 3 initiation steps.
• The mRNA is minutes or seconds short,
• .In eukaryotes The Lysosomes is cytoclasms and MEt is removed after initation
• Also requires the 9 other factors with with RNA stability.

Structure and function

• The protein has function of a 3d state and are amino acids are linked

Proteins

• The three- dimensional (3D) structure, of a protein by a chain of amino connected through a peptide.
• Protein primarily stabilized with the following; hydrophobic bonds between nonpolar side chains, hydrogen bonds between polar side chains and peptide bonds. Forces that stabilizes secondary structure.
• Polypeptide chain helps and controls folding.

More facts about protiens

• Two enzymes: isomerases that catalyse through protein folding that helps the peptide bonding of the two molecules in the two.
• Important step that make polypeptide clear, that can move proteins through membrane and terminate sequences and activation for other things.

Modification of Portiens

• Sugars proteins modified through glycosylation with translation process.
• Some eukaryotic cells are attached with lipid' to polypeptide chain
• improperly folded products that get degraded by the degradation pathways.

Degraded Lovalization

• Alpha 1 Antitrypsin deficiency (AIM 613490). Misfoldings or changes lead to liver or lung damage. Changed for proper degradation of liver in ER. Changes it not secrete and not perform actions.

AMyloid

• Abnormal or extra cell deposits found in body that are structured in beta sheet.
• Are formed to make soluble of form insoluble,
• Degradation can occur by disease through a specific chain type.
• Diseases like huntigntons may occur, which happens with expansion.