文档介绍：Role of Genetic Polymorphisms in Responses to Toxic Agents
Definitions
“Forward genetics” and toxicology
“Reverse genetics” and toxicology
Genetic markers
SNPs and their use in toxicology
Ethical, Legal and Social Issues (ELSI)
自然灾害给我们带来了什么
“Toxicology is concerned with the interaction between xenobiotics and biological molecules directly or indirectly coded in the DNA, and can be regarded as a branch of GENETICS.”
Michael . Festing (2001)
Gregor Mendel (1822 – 1884)
自然灾害给我们带来了什么
TERMINOLOGY
Gene: A sequence of DNA bases that encodes a protein
Allele: A sequence of DNA bases
Locus: Physical location of an allele on a chromosome
Linkage: Proximity of two alleles on a chromosome
Marker: An allele of known position on a chromosome
Distance: Number of base-pairs between two alleles
centiMorgan: Probabilistic distance of two alleles
Phenotype: An outward, observable character (trait)
Genotype: The internally coded, inheritable information
Penetrance: No. with phenotype / No. with allele
Modified from . Ramoni, Harvard Medical School
自然灾害给我们带来了什么
The 80s Revolution and
the Human Genome Project
Genetic Polymorphisms: naturally occurring DNA markers that identify regions of the genome and vary among individuals
The intuition that polymorphisms could be used as markers sparkled the revolution
On February 12, 2001 the Human Genome
Project announced the completion of a first
draft of the human genome and declared:
“A SNP map promises to revolutionize both
mapping diseases and tracing human history”
SNP are Single Nucleotide Polymorphisms – subtle
variations of the human genome across individuals
Modified from . Ramoni, Harvard Medical School
自然灾害给我们带来了什么
DISTANCES ON A GENETIC MAP
Physical distances between alleles are base-pairs
But the recombination frequency is not constant
A useful measure of distance is based on the probability of recombination: the Morgan
A distance of 1 centiMorgan (cM) between two alleles means that they have 1%