Saudi Genome Program Lecture Notes PDF

Lecture 5 Genome Projects Get ready for an exciting journey into the Saudi Genome Program! Lecture 9 Introduction Prepared by: Amjad Alrebdi Revised by: Dr. Hadil Alahdal Dr. Hadil Alahdal Genome...

Lecture 5 Genome Projects Get ready for an exciting journey into the Saudi Genome Program! Lecture 9 Introduction Prepared by: Amjad Alrebdi Revised by: Dr. Hadil Alahdal Dr. Hadil Alahdal Genome What is a genome? A genome is an organism's complete set of DNA. Where is it located in eukaryotes? What about mitochondrial DNA?  Genome vs Gene Genome Gene millions to billions of base pairs ranging from a few hundred base pairs to several thousand base pairs includes functional as well as non-function A gene is a dedicated functional piece of DNA DNA. the genome comprises coding as well as a gene encodes either structural or functional noncoding introns, intervening sequences, proteins pseudogenes, jumping genes, conserved sequences, and other DNAs. Only a single genome is present in an organism. Several hundred to thousand genes are present in an organism’s genome. A genome is an entire DNA present in the A gene is a short stretch of DNA. nucleus of a cell.  The Human Genome The human genome is the entire genetic material that makes up humans, which is known as DNA. The genome is found in every cell nucleus in the human body. The human body contains about 100 trillion cells. The human genome contains a unique sequence of DNA of 3 billion pairs of nucleotide bases, more than 99% of which are similar in all individuals. Each individual has millions of differences — known as variables — that differ from the sequence of reference. The proportion of differences between humans represents less than 1% of the genetic material. However, that small, different part of the genome between humans is one of the most unique aspects of the world, reflecting the different color of the eyes, hair, skin, etc. Although most of these differences are harmless, some may cause diseases, diseases predisposal and affect our response to treated drugs.  Chromosomes In the nucleus of each cell, the DNA molecule is packaged into thread- like structures called Chromosomes. Each chromosome is made up of DNA that is tightly coiled many times around proteins called histones that support its structure. Each chromosome has a constriction point called the centromere, which divides the chromosome into two sections, or “arms.” The short arm of the chromosome is labeled the “p arm”, while the long arm is labeled the “q arm”. The location of the centromere on each chromosome gives the chromosome its characteristic shape and can be used to help describe the location of specific genes.  Chromosomes In humans, each cell normally contains 23 pairs of chromosomes, for a total of 46 chromosomes. Twenty-two of these pairs, called autosomes, look the same in both males and females. The 23rd pair, i.e. the sex chromosomes, differs between males and females. Females have two copies of the X chromosome, while males have one X and one Y chromosome. https://www.nature.com/articles/d41586-021-02873-0 Variants A gene variant is a permanent alteration in the DNA sequence that makes up a gene, such that the sequence differs from what is found in most people. Variants range in size; they can affect anywhere from a single DNA building block (base pair) to a large segment of a chromosome that includes multiple genes. Gene variants can be classified in two major ways: ▪ Hereditary Variants are inherited from a parent and are present throughout a person’s life in every cell in the body. ▪ Also called Germline Variants; because they are present in the parent’s egg or sperm cells, which are also called Germ Cells. ▪ Acquired (or Somatic) Variants occur at some time during a person’s life and are present only in certain cells, not in every cell in the body. ▪ These changes can be caused by environmental factors: such as ultraviolet radiation from the sun, or can occur if an error is made; as the DNA copies itself during cell division. ▪ Acquired variants in somatic cells cannot be passed to the next generation.  History of Genome Sequencing First sequenced nucleic acid- Sequencing of the first biological RNA in 1965— the alanine transfer RNA from yeast First RNA viral genome sequenced (Bacteriophage MS2) in 1976. First DNA viral genome sequenced (Bacteriophage Phi X174) in 1978 developed the first DNA sequencing method that utilised radiolabelled partially digested fragments called “chain termination method”. This method Frederick Sanger went on to dominate the sequencing world for the next 30 years! The first organism to have its entire genome sequenced was (Haemophilus influenza) in 1995 First human genome project Other human genome projects The direct blotting electrophoresis system GATC1500.  Timeline: Organisms that have had their genomes sequenced Visit the following link: https://www.yourgenome.org/facts/timeline-organisms-that-have-had- their-genomes-sequenced Why did they not include : (Bacteriophage MS2) in 1976? (Bacteriophage Phi X174) in 1978? Human Genome Projects Human Genome Project 1000 Genomes Project 100,000 Genomes Project ENCODE GenomeAsia 100k Korean Genome Project Cancer Genome Project Genome Project- Write Saudi Genome Project  Saudi Human Genome Program Saudi Genome Program, whose central laboratory was inaugurated by his royal highness the crown prince in 2018, is one of the pioneering national programs and the largest genome initiative in the middle east. Launch of the Saudi Genome Program implemented by King Abdulaziz City for Science and Technology (KACST) is a testament to the Government’s attention to the nations’ healthcare services. Scientists and technicians from KACST working on the Saudi Human Genome Program  Vision Mission To achieve global To determine the variants leadership in the field of underlying genetic disease in the diagnostics to detect and Kingdom of Saudi Arabia, localize prevent genetic diseases. and develop genetic sequencing technologies, the field of genomics and bioinformatics in order to lay the foundation of personalized medicine. Saudi Genome Program Objectives: Determining the variants underlying genetic disease in the Kingdom of Saudi Arabia Limiting and preventing the genetic diseases in the Kingdom of Saudi Arabia Establishing and developing genetic sequencing technologies and the field of genomics and bioinformatics Building a genetic database for the Saudi population. Enabling scientists and researchers to benefit from the genetic information in the program. Developing diagnostic and prevention tools to reduce the incidences genetic diseases. Improving treatment methods based on the patient’s genetic makeup. Creating the foundation for personalized medicine in the Kingdom. Training national cadres in the field of genomics.  Genetic Disorders in Saudi Arabia Genetic disorders can be inherited and often show up at birth or early childhood. Their prevalence is higher in Saudi Arabia due to common consanguinity, significantly impacting patients, families, and the national healthcare system.  Genetic Diseases in the Kingdom of Saudi Arabia: Because of consanguineous marriages and other population characteristics, many disease-causing mutations are specific to the Saudi population and unlikely to be discovered by research conducted abroad. Hence, studying the basis of genetic diseases within the Kingdom is critical to solving undiagnosed cases and understanding the genetic landscape and disease spectrum in the Saudi population. https://www.frontiersin.org/journals/genetics/articles /10.3389/fgene.2023.1243518/full Premarital Screening Program: The efforts of the Saudi Genome Program have led to the identification of 7,500 variants of which 3,000 are novel mutations causing 1,230 rare genetic disorders among Saudi population. Utilizing this data, a customized technology was developed (SNP-array). This technology is designed to screen for these disease variants in Saudi individuals. It includes well-known inherited disease mutations in addition to those unique to the Saudi population.  Premarital Screening Program benefits: A platform has been established to enable screening of couples at a national level in collaboration with the Ministry of Health. The array is also extremely useful for early diagnosis of disease in newborns and will be implemented for this purpose in the next phase. Early diagnosis of diseases such as Sickle Cell Anemia, Cystic Fibrosis, Retinal Dystrophy, Hearing Loss, many metabolic diseases, liver failure etc., can benefit from early intervention. The application of this array has enormous potential in early detection and intervention for disorders resulting in disability. The premarital Screening Program enables efficient genetic counselling for couples in order to make informed decisions, and to prevent giving birth to affected children.  The Genome sequencing facilities include using the following Technologies technologies: Used: - Illumina NovaSeq for whole genome whole exome sequencing - Ion Proton and S5 XL for whole exome and gene panels sequencing - Sanger Sequencing for single DNA fragment sequencing. - Genotyping SNP array for calling a selected set of variants Bioinformatics and data analysis Primary Analysis: includes reading the genomic signals and signal processing. After that, the base calling step is conducted to transform the signals into strings specifying the sequencing of nucleotides in the genomic fragments. Secondary analysis: includes the alignment of the reads to the reference human genome. This step is also referred to as reference-based assembly where the subject genome is reconstructed by mapping to a reference genome. After each individual read is mapped, the reads alignments at that locus are adjusted. Finally in this phase, the variant caller scans the candidate positions including mutations and differentiates the real mutations using statistical models from sequencing errors. ACHIEVEMENTS Visit the website https://shgp.kacst.edu.sa/index.en.h tml#home  Next Phase Improving treatment methods based on the patient’s genetic makeup (personalized medicine). Early detection of some chronic diseases, and then development of the appropriate treatment plan. Pre-implantation genetic screening Fetal screening. Newborn screening. Homework Read and summaries the main findings of the following article http://jbcgenetics.com/index.php?mno=138347 https://humgenomics.biomedcentral.com/articles/10.1186/s40246- 024-00662-0