Introduction to Genetics (Ross and Wilson, 2018) PDF

# **Introduction to Genetics** ## **Chromosomes, Genes and DNA** - Chromosomes: 476 - Genes: 477 - DNA: 477 - Mutation: 477 - Protein Synthesis: 478 - Messenger Ribonucleic Acid: 478 - Cell Division: 480 - Mitosis : 480 - Meiosis: 480 - The Genetic Basis of Inheritance: 481 - Autosomal...

# **Introduction to Genetics** ## **Chromosomes, Genes and DNA** - Chromosomes: 476 - Genes: 477 - DNA: 477 - Mutation: 477 - Protein Synthesis: 478 - Messenger Ribonucleic Acid: 478 - Cell Division: 480 - Mitosis : 480 - Meiosis: 480 - The Genetic Basis of Inheritance: 481 - Autosomal Inheritance: 481 - Sex-Linked Inheritance: 482 - Ageing and Genetics: 483 - Genetic Basis of Disease: 484 - Cancer: 484 - Inherited Disease: 485 - Review and Revise: 485 ## **Section 4: Protection and Survival** ### Chromosomes, Genes and DNA - Nearly every body cell contains, within the nucleus, an identical copy of the entire complement of the individual's genetic material. - Two important exceptions include red blood cells, which have no nucleus, and gametes or sex cells. - Chromatin is diffuse and hard to see in a resting cell under the microscope. - When the cell prepares to divide, the chromatin is collected into highly visible, compact, sausage-shaped structures called chromosomes. - Each chromosome is one of a pair, one inherited from the mother and one from the father. - Human cells have 46 chromosomes that can be arranged into 23 pairs. - A cell with 23 pairs of chromosomes is termed diploid. - Gametes (sperm and ova), with only half the normal complement (23 chromosomes instead of 46), are described as haploid. - Chromosomes belonging to the same pair are called **homologous chromosomes**. - The complete set of chromosomes from a cell is its **karyotype**. ### Chromosomes - Each pair of chromosomes is numbered, with the largest pair being number 1. - The first 22 pairs are collectively known as **autosomes**. - The **sex chromosomes** are the pair in the 23rd position and are the pair that determines the individual's gender. - The chromosomes within each pair contain the same amount of genetic material, however the sex chromosomes are not necessarily the same size. ### The Y Chromosome - The Y chromosome in males is much shorter than the X chromosome, and is only carried by males. - A child inheriting two X chromosomes is female. - A child inheriting an X from his mother and a Y from his father is male. ### Chromosomes and DNA - Chromosomes are made of a tightly wound strand of DNA, along with supporting proteins called histones. - There is 2 meters of DNA per cell. - Each end of the chromosome is capped with a length of DNA called a telomere, which seals the chromosome and is structurally essential. - During replication, the telomere is shortened and is repaired with an enzyme called telomerase. - Reduced telomerase activity with age is related to cell senescence. ### Genes - 99% of the cell's DNA does not actually code for protein. - Filler DNA contains signals to stop and start protein synthesis. - DNA sequences that code for proteins are found along the length of the DNA, interspersed with filler DNA, and are called **genes**. - Each gene allows the cell to make a specific protein. - The human genome contains about 20,500 genes. ### DNA - DNA is a double-stranded molecule, made up of two chains of nucleotides. - Nucleotides consist of a sugar, a phosphate group, and a base. - The DNA molecule is likened to a twisted ladder. - The uprights are formed by alternating chains of deoxyribose, and phosphate units. - Each base is linked to the sugar and each base binds to another base on the other sugar/phosphate chain, forming the rungs of the ladder. - The two chains are twisted around one another, giving a double helix(twisted ladder) arrangement. - The double helix is further twisted and wrapped around histones, the structural proteins that are important in maintaining the heavily coiled three-dimensional shape of the DNA. - DNA-histone material is called chromatin. ### The Genetic Code - DNA carries a huge amount of information that determines all the biological activities of an organism, and is transmitted from one generation to the next. - Information is kept in the bases within DNA. - There are four bases: - Adenine (A) - Guanine (G) - Thymine (T) - Cytosine (C) - They are arranged in a precise order along the DNA molecule, making a base code that can be read when protein synthesis is required. - Each base pairs with a base on the other strand in a predictable way. - Adenine always pairs with thymine and cytosine always pairs with guanine. - The bases on opposite strands run down the middle of the helix and bind to one another with hydrogen bonds. ### Mitochondrial DNA - Each body cell has, on average, 5000 mitochondria. - These mitochondria hold a quantity of DNA (mitochondrial DNA) which codes, for example, for enzymes important in energy production. - Mitochondrial DNA is passed from one generation to another via the ovum. - The offspring’s mitochondrial DNA is inherited from the mother. - Certain rare inherited disorders that arise from faulty mitochondrial DNA are therefore passed through generations via the maternal line. ### Mutation - Means a heritable alteration in the normal genetic make-up of a cell. ### Chromosomes - The diagram shows a karyotype, the complete set of chromosomes from a cell ### Protein Synthesis - DNA holds the cell's essential biological information written within the base code in the center of the double helix. - Products of the information are almost always proteins. - Proteins are essential to all aspects of body function, forming the major structural elements, as well as the enzymes essential for all biochemical processes within it, - The building blocks of human proteins are about 20 different amino acids. - DNA is too big to leave the nucleus to create proteins. - An intermediary molecule is needed to carry genetic instructions from the nucleus to the cytoplasm, where proteins are made. - This is called **messenger ribonucleic acid **(mRNA). ### Messenger Ribonucleic Acid - mRNA is a single-stranded chain of nucleotides synthesized in the nucleus from the appropriate gene, whenever the cell needs to make the protein for which that gene codes. - RNA is different in structure to DNA in three main ways: - It is single-stranded, instead of double-stranded. - It contains the sugar ribose, instead of deoxyribose. - It uses the base **uracil**, instead of thymine. ### Gene Expression - Although all nucleated cells (except gametes) have an identical set of genes, each cell type uses only those genes related directly to its own particular function. - Example, the only cell type containing hemoglobin is the red blood cell, although all body cells carry the hemoglobin gene. - This selective gene expression is controlled by various regulatory substances, and the genes not needed by the cell are kept switched off. ### Cell Division - Most body cells are capable of division, even in adulthood. - Cell division usually leads to production of two identical diploid daughter cells by the process of **mitosis**, and is important in body growth and repair. - The production of gametes is different in that the daughter cells have only half the normal chromosome number (23 instead of 46). - The gametes are haploid cells. - Gametes are produced by a form of cell division called **meiosis**. - DNA replication takes place before mitosis and meiosis. ### DNA Replication - DNA is the only biological molecule capable of self-replication. - Mistakes in copying may lead to production of non-functioning or poorly functional, or cells that do not respond to normal cell controls. - This may lead to a tumor. - Accurate copying of DNA is therefore essential. - The initial step in DNA replication is the unfolding of the double helix and the unzipping of the two strands to expose the bases. - Both strands of the parent DNA molecule are copied. - The enzyme responsible for DNA replication moves along the base sequence, adding the complementary base to the newly forming chain - Each strand of opened bases becomes a double strand. - The end result is two identical DNA molecules. - As each new double strand is formed, other enzymes cause it to twist and coil back into its normal highly folded form. ### Mitosis - Described on page 47. ### Meiosis - The final step in gamete production. - When the male gamete (sperm cell) and the female gamete (ovum) unite, the resulting zygote is diploid. - Meiosis involves two distinct cell divisions, rather than one. - Meiosis produces four daughter cells, not two, all different from the parent cells and from each other. - This is the basis of genetic diversity and the uniqueness of each human individual. ### The Genetic Basis of Inheritance - Mixing up of parental genes during meiosis leads to the huge genetic variety of the human race. - It’s important to understand how genes interact to produce inherited characteristics. ### Autosomal Inheritance - Each of a pair of homologous chromosomes contains genes for the same traits. - Example, the ability to roll one's tongue is coded for by a single gene. - An individual inherits one chromosome of each pair from the father and one from the mother. - Paired genes are called **alleles**. - Corresponding alleles contain genes concerned with the same trait, but they need not be identical. - An individual may have: - two identical forms of the gene (homozygous). - two different forms of the gene (heterozygous). ### Co-dominance - For some traits, there can be more than two alleles that code for it, and more than one allele can be dominant. - Example: inheritance of A and B type antigens on the surface of red blood cells, determined clinically as the ABO system of blood grouping. - There are three possible alleles. - One allele codes for the production of A type antigens. - The other allele codes for the production of B type antigens. - There is a third allele that codes for no antigen at all. - An individual may have any combination of two of these three alleles: - AA, AB, BB, Ao, Bo or oo - Both A and B are dominant. - O is recessive. ### Sex-Linked Inheritance - The Y chromosome is much smaller than the X chromosome. - The Y chromosome carries only 200 genes, compared with the X chromosome’s 2000. - The X chromosome’s genes are involved in the development of male-specific characteristics. - Most of the genes on the X chromosome do not have a corresponding gene on the Y chromosome, so males only have one copy of most of the genes on their sex chromosomes. - Traits coded for on the section of the X chromosome that has no corresponding material on the Y are said to be sex-linked. - Example, the gene that codes for normal color vision is carried on X chromosomes only. - There is a rare recessive form of this gene that codes for red-green color blindness.. - If a female inherits a faulty copy of the gene, she is statistically likely to have a normal gene on her other X chromosome, giving normal color vision. - A female carrying the color blindness gene, may pass the faulty gene on to her children and is said to be a carrier. - If the gene is abnormal in a male, he will be color-blind, because, having only one X chromosome, he has only one copy of the gene. ### Ageing and Genetics - The number of times a cell can divide is somewhere between 50 and 60 divisions. - Telomere function repairs the telomeres (chromosome tips) following DNA replication, but it declines in function with age. - This restricts the number of cell replications possible, since without effective telomerase activity, the chromosomes become progressively shorter with each division; eventually they become too short to be replicated and the cell can no longer divide. ### The Genetic Basis of Disease - Cancer is caused by mutation of cellular DNA, causing its growth pattern to become disorganised and uncontrolled. - Cells acquire increasing numbers of mutations as they get older, which explains why the incidence of cancer rises sharply with increasing age. - Most cancer is due to acquired mutations caused by ageing or other risk factors, such as irradiation or exposure to mutagenic chemicals.. ### Inherited Disease - Many diseases, such as cystic fibrosis and haemophilia, are passed directly from parent to child via a faulty gene. - Many of these genes have been located by mapping of the human genome. - The gene for cystic fibrosis is carried on chromosome 7. - Other diseases, e.g. asthma, some cancers and cardiovascular disease, have a genetic component (run in the family). - **Phenylketonuria,** an example of an inborn error of metabolism, the gene responsible for producing the enzyme phenylalanine hydroxylase is faulty and the enzyme is absent. - This enzyme normally converts phenylalanine to tyrosine in the liver, but in its absence phenylalanine accumulates in the liver and overflows into the blood. - In high quantities, phenylalanine is toxic to the central nervous system. ### Mitochondrial Abnormalities - Mitochondrial DNA contains only 37 genes but defects in these genes can cause inherited disorders. - Defects commonly involve the central nervous system and skeletal or cardiac muscle. - Spontaneous mutations in this DNA can also occur in maturity, leading to the onset of disease in adults. - Mitochondrial mutations may be associated with some forms of important diseases, e.g. diabetes mellitus, Parkinson’s disease and Alzheimer’s disease. ## **Chromosomal Abnormalities** - A fault during meiosis produces a gamete carrying abnormal chromosomes (too many, too few, abnormally shaped or with segments missing). - Aberrations are lethal and a pregnancy involving such a gamete miscarries in the early stages. - Non-lethal conditions include Down’s syndrome and cri-du-chat syndrome. ### Down’s Syndrome - There are three copies of chromosome 21 (trisomy 21). - Meaning that an extra chromosome is present, caused by failure of chromosomes to separate normally during meiosis. - Individuals are usually short in stature, with pronounced eyelid folds and a flat, round face. - The tongue may be too large for the mouth and habitually protrudes. - Learning disability is present, ranging from mild to severe. - Life expectancy is shorter than normal, with a higher than average incidence of cardiovascular and respiratory disease, and a high incidence of early dementia. - Down’s syndrome is associated with increasing maternal age, especially over 35 years. ### Cri-du-Chat Syndrome - The characteristic meowing cry of an affected child. - Caused when part of chromosome 5 is missing. - It is associated with learning disabilities and anatomical abnormalities, including gastrointestinal and cardiovascular problems. ### Abnormalities of the Sex Chromosomes - The sex chromosomes fail to separate normally during meiosis, the daughter cells will have an incorrect number, too many or too few. - A child born with such an abnormality will not follow normal sexual development without treatment, and may have additional problems such as learning disability. #### Turner’s Syndrome - Usually associated with having only one sex chromosome (an X, as well as 22 normal pairs of autosomes). - The karyotype is therefore usually XO and affected individuals are female. - They have female external genitalia and ovaries, but are infertile. - The ovaries fail to develop during fetal life and secondary sexual characteristics do not develop at puberty unless oestrogen treatment is given. - Other features include short stature and coarctation of the aorta. - Intelligence is usually normal. #### Kinefelter’s Syndrome - The karyotype in this condition is XXY, so affected individuals are male. - The condition is more common than Turner’s syndrome. - Associated with a greater than average height and mild learning disability. - The genitalia are male, but the testes are underdeveloped, and individuals are infertile. - At puberty, development of feminine characteristics, such as enlarged breasts and rounded hips, is common. - There is no development of male secondary sexual characteristics unless testosterone treatment is given.