Patho Unit 2 #1 PDF

# UNIT II- Diseases are caused by defective genes and chromosomes. ## Pre-reg BSN Year 2 ### Learning objectives - Student will be able to: - Review the normal anatomical and physiological functions of the gene and define important terminologies in the genetic and chromosomal disorders - D...

# UNIT II- Diseases are caused by defective genes and chromosomes. ## Pre-reg BSN Year 2 ### Learning objectives - Student will be able to: - Review the normal anatomical and physiological functions of the gene and define important terminologies in the genetic and chromosomal disorders - Describe the sing gene disorders - Explain the chromosomal disorders - Illustrate the different features of hereditary disorders ### Introduction - Almost every cell in our body has 23 pairs of chromosomes, totaling 46. Our mother contributes half of our chromosomes, while our father contributes the other half. Autosomes refer to the initial 22 pairs of chromosomes. The X and Y chromosomes make up the 23rd pair. In each cell, females have two X chromosomes while males have one X and one Y chromosome. The chromosomes provide the body with all of the information it requires to grow and develop. Thousands of genes generate proteins that direct the body's development, growth, and chemical reactions on each chromosome. - A number of genetic illnesses with distinct traits are caused by chromosomal abnormalities and faulty genes. - With about 3 billion base pairs of deoxyribonucleic acid (DNA) in the human genome, it's not unexpected that faults in the genetic code (genetic mutations) might develop. - Genetic disease often leads to unviable embryos or babies with very short lifespans. - However, there are also survivable genetic diseases – for example, Down's syndrome, Klinefelter's syndrome, cystic fibrosis and Huntington's disease. Genetic diseases can be broadly classified into those affecting entire chromosomes (chromosomal disorders) and those affecting single genes (single-gene defects). ### References - [link to the first youtube video](https://www.youtube.com/watch?v=WAGjRcoolds) - [link to the second youtube video](https://www.youtube.com/watch?v=BI8ul2WeFFo) ### Human cell structure a 3D image - The image shows a human cell with its different components labelled. - The nucleus is located in the center of the cell and contains the nucleolus. - The cytoplasm surrounds the nucleus and contains the other organelles, - including ribosomes, mitochondria, Golgi apparatus, lysosomes, endoplasmic reticulum, and centrioles. - The cell membrane is the outermost layer of the cell. - The image also includes a 3D representation of a human cell. ### Genes and Chromosomes - **Genes are the basic units of inheritance in nature.** Genes are passed down the generations in a predictable manner and we receive roughly half of our genetic material from each parent. - **Genes are located in chromosomes.** The body cells have a constant number of paired chromosomes. - **The two chromosomes of a pair are known as homologous chromosomes.** In human body cells, there are 23 pairs of homologous chromosomes for a total of 46 chromosomes. - **Diagram of the DNA molecule and chromosome:** - It shows how DNA is packaged into chromosomes. - It also shows the hierarchical structure of DNA through to the chromosome. - DNA is a combination of 4 possible amino acids, bound in pairs, in a double helix structure. - Nucleotides are multiple segments of DNA base pairs. - Human DNA stretched out measures some 6 feet/1.8 meters. - **Diagram of the chromosome:** - It shows the p arm, q arm, centromere, and telomere of the chromosome. - It also shows the DNA molecule coiled around it. - **Diagram of the karyotype:** It shows the 22 autosomes numbered by size. The other two chromosomes, X and Y, are the sex chromosomes. - **The Structures of DNA and RNA Molecules** - RNA molecules usually exist as single polypeptide chains - DNA molecules have two polynucleotides spiraling around an imaginary axis, forming a double helix - In the DNA double helix, the two backbones run in opposite 5'→ 3' directions from each other, an arrangement referred to as antiparallel - One DNA molecule includes many genes - **Diagram of DNA and RNA:** - It shows the four nucleotide bases (adenine, guanine, cytosine, and thymine) in DNA. - It also shows the four nucleotide bases (adenine, guanine, cytosine, and uracil) in RNA. ### Terminologies - **Gene:** A segment of a DNA molecule that codes for the synthesis of a single polypeptide. - **DNA:** Deoxyribonucleic acid. Composed of nucleic acids, these molecules encode the genes that allow genetic information to be passed to offspring. - **Genome:** Term used to denote the entire DNA sequence (gene content) of a gamete, person, population, or species. - **Meiosis:** The type of cell division that occurs in sex cells by which gametes having the haploid number of chromosomes are produced from diploid cells. - **Messenger RNA (mRNA):** Type of RNA polymerase using DNA as a template. Contains the codons that encompass the genetic codes to be translated into protein. - **Mitosis:** Cell division that results in the formation of two cells, each with the same number of chromosomes as the parent cells, i.e., cell division that forms all new cells except sex cells. - **Aneuploidy:** A cell or individual with one or more missing or extra chromosomes - **Polyploidy:** is a condition in which the cells of an organism have more than two paired (homologous) sets of chromosomes. Most species whose cells have nuclei (eukaryotes) are diploid, meaning they have two sets of chromosomes—one set inherited from each parent. - **Prokaryotes:** are unicellular organisms that lack membrane-bound structures, the most noteworthy of which is the nucleus. Prokaryotic cells tend to be small, simple cells, measuring around 0.1-5 µm in diameter. - **Eukaryotes:** are organisms whose cells have a nucleus and other organelles enclosed by a plasma membrane. Organelles are internal structures responsible for a variety of functions, such as energy production and protein synthesis. - **Pedigree or genogram:** A diagram representing a family tree. - **X-chromosome:** The sex chromosome present in double dose in females (XX) and in single dose in males (XY). - **Y-chromosome:** The sex chromosome present only in males (XY). - **Acentric chromosome:** A chromosome that does not have a centromere and that is unable to participate properly in cell division; often the result of a chromosomal mutation during recombination - **Chromatid:** Either of two threadlike strands into which a chromosome divides longitudinally during cell division; each contains a double helix of DNA - **Chromatin:** The material of which the chromosomes of organisms other than bacteria (i.e., eukaryotes) are composed. It consists of protein, RNA, and DNA - **Chromosome:** the form in which genetic material is found in the nucleus of a cell; composed of a single DNA molecule that is extremely tightly coiled and usually visible only during the processes of mitosis and meiosis - **Chromosomal rearrangement:** Type of chromosome abnormality involving a change in the structure of the native chromosome and encompass several different classes of events: deletions, duplications, inversions; and translocations - **Chromosome breakpoints:** Locations on a chromosome where DNA might get deleted, inverted, or swapped around - **Chromosome map:** A diagram showing the locations of genes on a particular chromosome; generated through analysis of linkage experiments involving those genes. - **Karyotype:** A photomicrograph (photograph taken through a microscope) of all the chromosomes in a person, arranged in standard classification (from #1 chromosomes through to the sex chromosomes). - **Phenotype:** Phenotype is what you see - the visible or observable expression of the results of genes, combined with the environmental influence on an organism's appearance or behavior. The antigens (traits) that result from those genes that are directly expressed (can be directly antigen typed), e.g., group A in the ABO blood group system or D+C+E- c+e+ in the Rh BGS. Phenotype, therefore, is observable by nature. Every trait determined by a gene. **For examples:** Eye color, Hair color, Height, Sound of your voice, Certain types of disease. - **Genotype:** It's hard to provide concrete examples of genotype. The term just means "the genes a particular organism has." Any example of a genotype would just be a chart of a particular living thing's chromosomes, or DNA molecules responsible for various genetic traits. However, having certain genes does have observable results. **For example,** if you met someone with albinism you would know they most likely have a mutated TYR gene, because that's the most common cause of albinism. That mutated TYR gene is part of their genotype. Albinism is part of their phenotype. - **Mutation:** A permanent inheritable change in a single gene (point mutation) that results in the existence of two or more alleles occurring at the same locus. Blood group polymorphism has been caused by mutations occurring over long periods of time. - **Nondisjunction:** The failure of two members of a chromosome pair to disjoin during anaphase. For example, an offspring with the AB/O genotype can be produced if a group AB male mates with a group O female and nondisjunction happens in the father. - **Carrier:** A healthy individual who has one normal allele and one defective allele for a recessive genetic disease. ### Genetic disorder - **DEFINITION:** A genetic disorder is a disease caused in whole or in part by a change in the DNA sequence away from the normal sequence. Genetic disorders can be caused by a mutation in one gene (monogenic disorder), by mutations in multiple genes (multifactorial inheritance disorder), by a combination of gene mutations and environmental factors, or by damage to chromosomes (changes in the number or structure of entire chromosomes, the structures that carry genes). - **Cause 1:** - An error during meiosis causes a sperm cell or an egg cell to have some defect. - If one of these gametes is involved in fertilization, it usually results in miscarriage, but in a few cases, a baby will develop and be carried to term with a genetic disorder. - **Nondisjunction Causes:** - **Aneuploidy:** cells that have too many or too few chromosomes are aneuploid. - **Monosomy:** only 1 of a pair present - **Trisomy:** 3 instead of 2 present - **Cause 2:** - A defective gene present in one or both of the parents is inherited directly by the child causing a disorder. - These kinds of disorders are called **hereditary diseases** and follow the same rules of inheritance as other human traits. ### Incidence of Genetic Abnormalities - **Maternal Age** - At 25 years, 17% of eggs may have chromosomal abnormalities. At 40 years, up to 74% may contain abnormalities.. - **Spontaneous Abortion (Miscarriage)** - Two-thirds of all pregnancies are lost. These miscarriages are called spontaneous abortions. - Genetic mutation causes an estimated 60% of these spontaneous abortions. ### Hereditary Diseases Caused by Dominant Genes - Only one copy of the gene (from either parent) is needed for a person to have the disease. - A person with a dominant hereditary disease usually has at least one affected parent - Parents have a 50% chance of passing these types of diseases to children. ### Autosomal Dominant Disorders - **Neurofibromatosis (NF)** - Could be "Elephant Man's" disorder - As mild as tan spots on skin - Could cause severe deformities, tumors, even death - 1 in 3000 newborns - Mutation on chromosome 17 ### Hereditary Diseases Caused by Recessive Genes - Two copies of the defective gene must be inherited (one from each parent) - Affected persons usually have two non-affected parents who are carriers - Two carrier parents have a 25% chance of having a child with the disease ### What are the four types of genetic disorders (inherited)? - There are a number of different types of genetic disorders (inherited) and include: - **I. Single gene inheritance** - **II. Multifactorial inheritance** - **III. Chromosome abnormalities** - **IV. Mitochondrial inheritance** ### I. Single gene inheritance - Single gene inheritance is also called Mendelian or monogenetic inheritance. Changes or mutations that occur in the DNA sequence of a single gene cause this type of inheritance. - **Single-gene disorders have different patterns of genetic inheritance, including** - **autosomal dominant inheritance,** in which only one copy of a defective gene (from either parent) is necessary to cause the condition; - **autosomal recessive inheritance,** in which two copies of a defective gene (one from each parent) are necessary to cause the condition; and - **X-linked inheritance,** in which the defective gene is present on the female, or X-chromosome. X-linked inheritance may be dominant or recessive. ### 7 common single gene inheritance disorders - 1. Cystic fibrosis, - 2. Alpha- and beta-thalassemias, - 3. Sickle cell anemia (sickle cell disease), - 4. Marfan syndrome, - 5. Fragile X syndrome, - 6. Huntington's disease, and - 7. Hemochromatosis. ### II. Multifactorial inheritance - Multifactorial inheritance is also called complex or polygenic inheritance. Multifactorial inheritance disorders are caused by a combination of environmental factors and mutations in multiple genes. For example, different genes that influence breast cancer susceptibility have been found on chromosomes 6, 11, 13, 14, 15, 17, and 22. Some common chronic diseases are multifactorial disorders. ### 7 common multifactorial genetic inheritance disorders - 1. Heart Disease, - 2. High Blood Pressure, - 3. Alzheimer's Disease, - 4. Arthritis, - 5. Diabetes, - 6. Cancer, And - 7. Obesity. ### The contributions of genetic and environmental factors to human diseases - The diagram shows the different types of genetic disorders based on multifactorial and unifactorial inheritance: - **GENETIC** - Duchenne muscular dystrophy - Haemophilia - Osteogenesis imperfecta - Phenylketonuria - Galactosaemia - **ENVIRONMENTAL** - Club foot - Pyloric stenosis - Dislocation of hip - Peptic ulcer - Diabetes - Tuberculosis - Spina bifida - Ischaemic heart disease - Ankylosing spondylitis - Scurvy ### III. Chromosome abnormalities - In certain situations e.g., due to environmental radiation, food intake or internal genetic conditions, chromosomes may suffer damage or may change in numbers. The change in structure is called **structural chromosomal abnormality (or aberration)** and the change in number is called **numerical chromosomal abnormalities**. ### a. chromosomal abnormality - 1. Deletion - 2. Duplication - 3. Inversion - 4. Translocation ### b. Numerical chromosomal abnormalities - When one chromosome of the pair is absent, the condition is called **monosomy** (2n-1) for that chromosome e.g., **monosomy of chromosome 1.** - When a chromosome is present in three copies, this condition is called **trisomy** (2n+1) e.g., trisomy of chromosome X. It is important to notice that both monosomy and trisomy come under the broad category of aneuploidy. ### IV. Mitochondrial inheritance genetic disorders - This type of genetic disorder is caused by mutations in the non-nuclear DNA of mitochondria. Mitochondria are small round or rod-like organelles that are involved in cellular respiration and found in the cytoplasm of plant and animal cells. Each mitochondrion may contain 5 to 10 circular pieces of DNA. Since egg cells, but not sperm cells, keep their mitochondria during fertilization, mitochondrial DNA is always inherited from the female parent. ### Monosomy of chromosome 1. - The image shows different people with monosomy of chromosome 1. ### Chromosome and Gene Anomalies - **Down Syndrome (Trisomy 21)** Down syndrome is an anomaly of chromosome 21 that can cause **intellectual disability**, microcephaly, short stature, and characteristic faces. Diagnosis is suggested by physical anomalies and abnormal development and confirmed by cytogenetic analysis. Treatment depends on specific manifestations and anomalies. **The image shows the karyotype of a person with Down Syndrome.** - **Trisomy 18:** is caused by an extra chromosome 18 and is usually associated with intellectual disability, small birth size, and various congenital anomalies, including severe microcephaly, heart defects, prominent occiput, low-set malformed ears, and a characteristic pinched facial appearance. The image shows the karyotype of a person with Trisomy 18. The karyotype shows the extra chromosome 18. - **Trisomy 13:** is caused by an extra chromosome 13 and causes abnormal forebrain, midface, and eye development; severe intellectual disability; heart defects; and small birth size. The image shows the karyotype of a person with Trisomy 13. The karyotype shows the extra chromosome 13 ### Examples of mitochondrial disease include - **Leber's hereditary optic atrophy (LHON),** an eye disease; - **Myoclonic epilepsy with ragged red fibers (MERRF);** - **Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS),** a rare form of dementia. - **Image of a human eye with hyperemia:** It shows the hyperemia in the eye as a sign of Leber's hereditary optic atrophy (LHON). - The image of **MERRF (myoclonic epilepsy with ragged red fibers)** shows the ragged red fibers in muscle tissue. - The image of a human brain with a **stroke-like episode** in a person with MELAS (Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes). ### What is Mitochondrial encephalo myopathy, lactic acidosis, and stroke-like episodes (MELAS)? - **Mitochondrial** = Mutation in the mitochondria - **Encephalo**- = Occurs in the head - **Myopathy** = General term for muscle disease - **Lactic Acidosis** = The blood gets too acidic - **Stroke-like Episodes** = Brain-related symptoms of bleeding or blockage. ### References - [link to the Huntington's disease website](https://www.healthdirect.gov.au/huntingtons-disease) - [link to the hereditary diseases slide share](https://www.slideshare.net/E_neutron/hereditary-diseases-77472463) - [link to the chromosomes and genes website](https://www.w3spoint.com/chromosomes-and-genes) - [link to the breast cancer picture slideshow](https://www.medicinenet.com/breast_cancer_picture_s_slideshow/article.htm) - [link to the NCBI website](https://www.ncbi.nlm.nih.gov/books/NBK115545/)