МУТАЦИИ англ. СМИРНОВА.pptx
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Sources of Genetic Variation Smirnova S. N.
Review DNA is 3 billion base pairs long. It is found in the nucleus of each of our cells. • When DNA is loosely wrapped around proteins called histones in the nucleus, it is called Chromatin and looks like a loosely tangled mix of spaghetti • When wrapped around histones in an tightly organized fashion, the chromatin is now called chromosomes.
We can see chromosomes in this form during the M-phase in the cell cycle. Humans have 46 chromosomes • We can also say humans have 23 pairs of chromosomes • We can see and examine them when they are arranged in a picture ma called a karyotype DNA (Chromosomes) code for the various proteins our body’s need Proteins can be altered because of mutations. • They can influence our appearance • They are involved in bodily processes • Hey are involved in bodily repair
Variation - genetic diversity, differences within a species. Human variability, or human variation, is the range of possible values for any measurable characteristic, physical or mental, of human beings. Differences can be trivial or important, transient or permanent, voluntary or involuntary, congenital or acquired, genetic or environmental.
Variation means the differences in characteristics (phenotype) within a species. There are many causes of variation as this chart shows:
Variation consists of differences between species as well as differences within the same species. Each individual is influenced by the environment, so this is another source of variation. genotype + environment = phenotype
There is considerable variability between individuals and between populations in their ability to adjust to the environmental stresses of high mountain regions. Usually, the populations that are most successful are those whose ancestors have lived at high altitudes for thousands of years. This is the case with some of the indigenous peoples living in the Andes Mountains of Peru and Bolivia as well as the Tibetans and Nepalese in the Himalaya Mountains. The ancestors of many people in each of these populations have lived above 13, 000 feet (ca. 4000 meters) for at least 2, 700 years. Her cheeks are red primarily due to increased blood flow near the skin surface. More red blood cells help her get oxygen to the tissues of her body. Peruvian Indian woman and Tibetan man
Phenotypic Variability Human genetics can be complicated, especially when you think about all of the different types of inheritance that are possible. At least there are some genetic conditions that are simple, like autosomal dominant conditions, right? Well, not so fast! We are talking about biology here, and one of the most important lessons I've learned over the years is that there is almost always an exception to the rule when it comes to biological systems. This applies to dominant human conditions as well. You see, when a person inherits a dominant allele, we expect them to exhibit a particular trait or set of traits that constitute a condition or syndrome. However, what we find in reality is that a dominant allele will affect different people in different ways, and even people with the same specific genotype can show phenotypic variability, or a range of different phenotypes. There are two technical terms that geneticists use to describe phenotypic variability: expressivity and penetrance.
Expressivity is the extent to which a trait or condition is expressed. In other words, expressivity refers to how mild or severe the phenotype is and which of the hallmarks of the condition are present in the phenotype. Many genetic conditions have been identified as a set of characteristics that occur together. These conditions are called syndromes and are groupings of recognizable characteristics that occur together and have a common cause. Genetic syndromes are often quite variable in their expressivity. Let's take, for example, the rare autosomal dominant syndrome Peutz-Jegher's Syndrome, which we will call PJS for short. PJS is a syndrome where affected individuals have the following characteristics. The first characteristic is dark spots reminiscent of freckles in and around the mouth and lips and sometimes on the fingers and toes. The second characteristic is high numbers of gastrointestinal polyps, which are basically outgrowths of the intestinal wall. In this simplified diagram, you can see a polyp growing out from the intestinal wall and an instrument that a doctor can use to remove polyps from the gastrointestinal tract. The third characteristic of PJS is an increased risk of various types of cancer. All of these characteristics are hallmarks of PJS, but there is a lot of variability among individuals for each of these characteristics, and not every PJS patient exhibits all three. Some people may have the dark spots around their mouth and lots of gastrointestinal polyps but never develop cancer, while others may have few polyps, no dark spots, and develop several cancerous tumors in their lifetime.
Expressivity doesn't just refer to the number of characteristics a patient has; it can also refer to the severity of any single characteristic or the severity of the entire condition as a whole. For example, in PJS, the number of gastrointestinal polyps varies significantly from patient to patient. Some have only a few, while others may have hundreds over the course of their lifetime. In addition, a general susceptibility to multiple types of cancers introduces an inherent variability into this condition. It's difficult to determine whether the severity of something like cancer risk changes from patient to patient. However, it is clear that some patients develop more severe and aggressive forms of cancer than others, so in this sense, the severity of the resulting cancers is variable.
The proportion of individuals with a mutation causing a particular disorder who exhibit clinical symptoms of that disorder; a condition (most commonly inherited in an autosomal dominant manner) is said to have complete penetrance if clinical symptoms are present in all individuals who have the disease-causing mutation, and to have reduced or incomplete penetrance if clinical symptoms are not always present in individuals who have the disease-causing mutation. The probability of a gene or genetic trait being expressed. "Complete" penetrance means the gene or genes for a trait are expressed in all the population who have the genes. "Incomplete" penetrance means the genetic trait is expressed in only part of the population. The percent penetrance also may change with the age range of the population.
Recombination The crucial events of meiosis are those which are responsible for recombination, which means that the combinations of alleles passed by individuals to their offspring differ from those that were passed to the individuals by their parents. This helps to a level of genetic variation.
MUTATION Mutation = Change Biologists use the term “mutation” when talking about any change in the genetic material. Not all result in a change in phenotype. There are two major types of mutations: Macromutations - Also called macrolesions and chromosomal aberations. Involve changes in large amounts of DNA. Micromutations - Commonly called point mutations and microlesions.
Mutation It is defined as a change in the DNA sequence of a cell's genome. Mutations can be divided into 3 classes or categories: Genome mutations: Mutations that affect the number of chromosomes. Chromosome mutations: Mutations that alter the structure of individual chromosomes. Also known as Gross mutations. Gene mutations: Mutations that alter individual genes.
All 3 types of mutations occur quite often in many different cells. However, if a mutation occurs in a germline cell, it may be passed on to future generations. On the other hand somatic mutations occur by chance in a subset of cells in certain tissues and result in somatic mosaicism that cannot be transmitted.
The cells that make up the human body can broadly be divided into two sorts. The germ line cells, which are the sperm in males and eggs in females, while somatic cells include all the other remaining cells (which form muscles, bone, skin, brain etc. ). Mosaicism occurs when a person has 2 cell populations each with distinct genetic information. So, one population contains “normal” genetic material, whilst the other population may have a mutation or other genetic abnormality. Mosaicism can affect both germ line cells and somatic cells.
Somatic mosaicism There a number of genetic disorders that display somatic mosaicism. The effects of somatic mosaicism are not usually passed on to offspring as the germ line cells are all normal. The asymmetrical skin pigmentation
Gene mutations which affect only one gene Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons ↓ Pro-Glu-Cys-Gly Amino acids Substitution mutation GGT CAC CTC ACG CCA ↓ CCAGUGGAGUGCGGU ↓ Pro-Arg-Glu-Cys-Gly Substitutions will only affect a single codon
Aneuploidy is a condition in which the number of chromosomes in the nucleus of a cell is not an exact multiple of the monoploid number of a particular species. An extra or missing chromosome is a common cause of genetic disorders including human birth defects. Some cancer cells also have abnormal numbers of chromosomes. Aneuploidy originates during cell division when the chromosomes do not separate properly between the two cells. This generally happens when cytokinesis begins while karyokinesis is still under way.
Trisomy 21 (Down syndrome) is one of the best-recognized and most common chromosome disorders. It is the single most common genetic cause for mental retardation. The incidence of Down syndrome is approximately 1/800 newborns. The risk for having a child with trisomy 21 Down syndrome increases with maternal age.
Common sex chromosome abnormalities Sex chromosome abnormalities have less severe clinical anomalies than those associated with comparable autosomal imbalances. This diﬀerence can be attributed to genetic inactivation of all but one X-chromosome in those cases where multiple copies are present, and the relatively low gene content of the Y-chromosome. Sex chromosome aneuploidy is relatively common, with overall frequency of about 1 in 500 live births. Some (XXX, XXY, XYY) are relatively frequent in newborns but rare in spontaneous abortions. Monosomy X (Turner syndrome), in contrast, is one of the most common chromosome abnormalities seen in spontaneous abortions but relatively rare in newborns.
Triploidy is a disorder that arises at conception when a baby starts life in the womb with a complete extra set of chromosomes. Chromosomes are the microscopically small structures in the nucleus of the body’s cells that carry genetic information. Most people have two sets of 23 chromosomes, making 46 in all. Babies who have too many chromosomes or too few are at increased risk of developmental problems and birth defects. Babies with triploidy have an entire extra set of chromosomes, making 69 in all. Most studies seem to suggest that around two thirds of triploid pregnancies are boys, while around one third are girls.
Can a baby live with triploidy? Very occasionally, babies with triploidy are born and live for a few hours, days or weeks. One baby reported in the medical literature lived to 10½ months, but this is very rare. Two out of three pregnancies miscarry in the first trimester and almost all other babies die later or are stillborn. Is triploidy rare? At conception, triploidy is thought to affect an estimated one to three per cent of confirmed pregnancies.
What happens in triploidy? A baby boy or girl with triploidy starts life in one of three ways. • The egg is fertilised by a sperm with a double set of chromosomes (diandry) • The egg is fertilised by two sperm (dispermy, a type of diandry) In both forms of diandry, the fetus has two sets of chromosomes from the father and a single set of the mother’s chromosomes. Diandric pregnancies tend to have a large placenta. The baby is usually a good size but is more likely to miscarry during the first trimester. • The egg-producing cells fail to divide properly and so the mature egg contains a double set of chromosomes (digyny). The baby has two sets of maternal chromosomes and a single set of paternal chromosomes. Digynic pregnancies 3 have a small placenta and the baby and particularly the body is usually severely growth restricted. Compared with diandric pregnancies, more babies with digyny live into the second trimester and studies have shown that four out of five babies who lived for more than a month after birth were digynic.
Teratogen: Any agent that can disturb the development of an embryo or fetus.
Periods of Fetal Development