GEE Lecture 1 Basic Mendelism PDF

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Lecture 1 : Basic Mendelism : Introduction : • Trillions and Trillions of cells and 2 meters of DNA in every cell. 23,000 genes in the human genome. • Life expectancy has improved dramatically and keeps on improving with better healthcare. The diseases we die of today have a strong genetic component. Looking at cells for mutations that cause cancer before the tumor is formed. Cost of sequencing has gone down dramatically : 10,000 x since 15 years. First sequencing around 2000 cost 100 million dollars, nowadays 1000. Soon, we will be sequencing the genes of all the baby’s in the world. However, the cost of understanding DNA with computing has gone up • The 100,000 genomes project that started in 2012 : goal to sequence the entire genome of 100,000 NHS patients which has today been reached. These people can then be followed throughout their life, seeing what diseases they have and their genetic weaknesses. • By sequencing DNA, we can see what genes are weaker. Looking at cells for mutations that cause cancer before the tumor is formed. • CRISPR : technique consisting of cutting out and replacing a damaged piece of DNA has successfully reversed a genetic deafness in mice, identical to a gene found in humans. • Agricultural genetics has revolutionized commerce. Without it, we would starve (corn yield in US)... • Evolution : descent with modification. 1837 : sketch of evolutionary tree by Darwin

Beginning of genetics : • Strong Political overtones – early history of genetics is empty : cutting off mice’s tails at UCL Eugenics : the selection of desired heritable characteristics in order to improve future generations – genetic selection controversial. • Something that is inherited is not necessarily genetic – prince William’s ears vs crown Pellagra : disease that causes flakey skin and blindness can be traced in families going back 3 generations, deficiency of vitamin A but not genetic, due to a poor environment. • A scientist attacked Darwin’s theory of natural selection with Darwin’s own theory of blending inheritance ( : mixing of bloods of each parent ) that would average out any beneficial characteristic before natural selection had time to act • Gregor Mendel first proposed that the gene was a particle rather than a fluid Worked on the self-fertilizing hermaphrodite pea flower – kept as pure lines by plant breeders 1st experiment : Crossed Yellow X Green -> Yellow Offspring 2nd experiment : Self fertilized Yellow Offspring -> 3 Yellow to 1 Green 3rd experiment : Self fertilized 2nd Green Offspring -> Pure Green Offspring 4th experiment : Self fertilized 2nd Yellow Offspring -> 1/3 Pure Yellow Offspring and 2/3 produced Yellow and Green Offspring. What was passed on each generation was not the character itself, but information, coded into particles that do not blend. Adult peas have two particles for each character; pollen and egg only one - meet at fertilization.

Terminology : • Law of segregation : alleles for each gene segregate from each other so that each gamete carries only one allele for each gene. • When two gametes meet they make a zygote. On DNA, locus for pea color with 2 variants or alleles ( sometimes dozens of different alleles ). Some alleles are “dominant”, others “recessive”. • 2 copies of the same allele “homozygote” and one of each “heterozygote”

Mendelian Inheritance in Humans : • For a particular illness : we are not studying the gene for depression but rather a gene of unknown function which when it goes wrong leads to such symptoms. • For humans, we can’t set up experimental mating’s, depend on nature’s experiments We can look at pedigrees ( diagram that depicts the biological relationships between an organism and its ancestors ), royal families. Males are squares and Females circles. Those with affected character are circled in. To show mating between 2 family members, we draw two lines – consanguineous mating. • Dominant Inheritance easier to study than recessive inheritance ( although if they are very harmful they disappear quickly as they kill all the carriers ) Brach pedigrees : discovery in an isolated village in Norway – shorter fingers and toes. Every affected person has an affected parent. Every individual affected has got one copy of the dominant allele. Everyone unaffected has got 2 copies of the recessive. If one of your parents is affected, then ½ of you having it. • Recessive inheritance : affected child born to normal parents, can skip generations. If the 2 parents have a single copy of the disease ¼ of children affected. Cystic Fibrosis : Recessive inheritance : homozygote for 2 alleles to express themselves. If a child is affected then both parents heterozygotes. Cousin marriages are at a higher risk. Genetic counselling : probability of having an affected child. If one child affected, then further children have a one in four chance of being affected. Now we can directly examine DNA sequence. • Each of us have 2-3 recessive genes that we would die of if we had them as homozygote....