Component regions of the genome
This presentation is the property of its rightful owner.
Sponsored Links
1 / 21

Component Regions of the Genome PowerPoint PPT Presentation

  • Uploaded on
  • Presentation posted in: General

Component Regions of the Genome.

Download Presentation

Component Regions of the Genome




Presentation Transcript

Component regions of the genome

Component Regions of the Genome

The genome is composed of genes and the DNA between the genes (intergenic regions). The genes are divided into untranslated and translated regions. The translated regions are composed of exons (blue) and introns (green). The promoter region (purple) is located in the untranslated region of the gene.

Structure of dna

Structure of DNA

DNA is composed of 2 strands, each composed of a 5-carbon sugar (deoxyribose), a phosphate group (PO4), and a nucleotide base. One strand runs in a 5´ to 3´ direction, while the other runs in the 3´ to 5´ direction. Two of the bases (the purines, shown in blue) are larger than the others (the pyrimidines, shown in green) and are represented by capital letters.

Distribution of dna according to function

Distribution of DNA According to Function

Linkage disequilibrium

Linkage Disequilibrium

Linkage disequilibrium (LD) is a measure of the likelihood of a SNP and an unknown gene to be inherited together. If a SNP is located close to the unknown gene, there is a high LD. If the SNP and the unknown gene are farther apart, there is a greater chance that they will not be inherited together (low LD).

Alternative splicing

Alternative Splicing

The pre-mRNA contains the introns and the exons encoded in the DNA. For the mRNA to produce a functional protein, the introns must be removed. In removing the introns, a variety of potential exon combinations are possible, ie, different combinations of exons may be joined together to generate different forms of the same protein.

Component regions of rna

Component Regions of RNA

The leading and trailing regions, the 5´ and 3´ untranslated regions (UTR), are important for cellular positioning, message stability, and the efficiency with which protein can be made from the mRNA. The open reading frame codes for the protein.

Catabolism of uracil or thymine via dpd

Catabolism of Uracil or Thymine via DPD

Uracil is indicated by an H (green) and thymine by CH3 (blue). NADP+ = oxidized form of nicotinamide adenine dinucleotide phosphate; NADPH = reduced form of nicotinamide adenine dinucleotide phosphate.

Pathways for the anabolic and catabolic metabolism of 5 fu

Pathways for the Anabolic and Catabolic Metabolism of 5-FU

dTMP = thymidylate; dUMP = deoxyuridine monophosphate; FBAL = -fluoro-ß-alanine; FdUDP = fluorodeoxyuridine diphosphate; FdUMP = fluorodeoxyuridine monophosphate;FdUTP = fluorodeoxyuridine triphosphate; FUDP = fluorouridine diphosphate; FUdR = fluorodeoxyuridine; FUH2 = dihydrofluorouracil; FUMP = fluorouridine monophosphate; FUPA = -fluoro-ß-ureidopropionate; FUrd = 5-fluorouridine; FUTP = fluorouridine triphosphate; 5-FU = fluorouracil; TS = thymidylate synthetase.

Peripheral blood mononuclear pbm cell method for dpd activity assay

Peripheral Blood Mononuclear (PBM) Cell Method for DPD Activity Assay

5 fu pharmacokinetics in a dpd deficient patient

5-FU Pharmacokinetics in a DPD-Deficient Patient

From Diasio et al. J Clin Invest. 1988;81:47-51, with permission.

Genetic heritage of a completely dpd deficient woman

Genetic Heritage of a Completely DPD-Deficient Woman

A line through a symbol represents deceased members of the family, and the dashed symbols represent members who were alive but not tested for DPD status. The solid symbol represents complete DPD deficiency, the half-filled symbols represent partial deficiency, and the open symbols represent control levels of DPD activity. A double line represents consanguineous marriage.


Dpd activity in a healthy population

DPD Activity in a Healthy Population

Lu et al. Cancer Res. 1993;53:5433-5438.

Differential distribution of dpd activity in women with breast cancer vs healthy controls

Differential Distribution of DPD Activity in Women With Breast Cancer vs Healthy Controls

Lu et al. ClinCancer Res. 1998;4:325-329.

Linear structure of the dpd protein

Linear Structure of the DPD Protein

Schematic of the location of the active site and various domains of the DPD protein. FAD = flavin adenine dinucleotide; Fe-S = iron-sulfur; FMN = flavin mononucleotide; NADP = oxidized form of nicotinamide adenine dinucleotide phosphate; NADPH = reduced form of nicotinamide adenine dinucleotide phosphate.

Stereoview of dpd protein with marked functional groups

Stereoview of DPD Protein With Marked Functional Groups

FAD = flavin adenine dinucleotide; FeS = iron-sulfur group; FMN = flavin mononucleotide; NADP = nicotinamide adenine dinucleotide phosphate.

Structural organization of human dpd gene dpyd

Structural Organization of Human DPD Gene (DPYD)

Bars represent the exons; intervening spaces represent the introns.

Johnson et al. Cancer Res. 1997;57:1660-1663.

Human dpyd alleles and location and relative frequency of selected variants

Human DPYD Alleles and Location and Relative Frequency of Selected Variants

Variations in the dpd gene detected by allele specific pcr

Variations in the DPD Gene Detected by Allele-Specific PCR

One primer (probe) was perfectly complementary to the wild-type (“normal”) sequence at the end of exon 14. The other was perfectly complementary to the sequence for the DPYD*2A variant at the same location. Perfect complementation is necessary for PCR amplification to proceed.

Johnson et al. Clin Cancer Res. 1999;5:2006-2011.

Optimization of running temperature for dhplc for dpyd

Optimization of Running Temperature for DHPLC for DPYD

DHPLC = denaturing high-performance liquid chromatography.

Ezzeldin et al. Ann Biochem. 2002;306:63-73.

Column retention time for wild type and variant dna of dpyd by dhplc

Column Retention Time for Wild-Type and Variant DNA of DPYD by DHPLC


5 fu conversion from prodrug to active anabolite or inactive metabolite

5-FU Conversion From Prodrug to Active Anabolite or Inactive Metabolite

A, 5-FU can enter the metabolic pathway that converts it to fluorodeoxyuridine monophosphate (FdUMP), which can be converted to fluorodeoxyuridine diphosphate (FdUDP), or can inhibit thymidylate synthetase (TS). Inhibiting TS prevents the conversion of deoxyuridine monophosphate (dUMP) to thymidylate (dTMP), blocking the proper formation of DNA. FdUDP can be converted to fluorodeoxyuridine triphosphate (FdUTP), which is added to the growing DNA strands, where it alters the proper functioning of the DNA, leading to cell damage and death. B, 5-FU is converted to fluorouridine diphosphate (FUDP), which can be converted to either fluorouridine triphosphate (FUTP) or FdUDP. C, Most of the administered dose of 5-FU is converted by a series of enzymes (of which DPD is the rate-limiting step) to inactive metabolites dihydrofluorouracil (FUH2), -fluoro-ß-ureidopropionate (FUPA), and -fluoro-ß-alanine (FBAL).

  • Login