醫(yī)學(xué)遺傳學(xué)：遺傳重點(diǎn)提綱A

1、Chapter 1 緒論第一部分Heredity： A procedure that living things duplicate themselves in a model similar to their parents Stability of living thingsVariability： The differences of individuals resulted from genetic recombination, environmental modification and genetic mutation Diversity of living thingsGenet

2、icsA SCIENCE concerned with variation and heredity in living organismsGene: The fundamental physical and functional unit of heredity, which carries information from one generation to the nextAllele: One of the different forms of a gene pair. At each autosomal locus an individual possessed two allele

3、s, one inherited from mum and one from dad. Genotype: The combination of alleles that an individual possesses.Phenotype : The physical characteristics of a cell or organism as defined by its genetic constitutionLinkage: The association of genes on the same chromosome.Recombination : The exchange of

4、corresponding chromosome parts between homologous chromosomes by breakage and reunion第二部分Genes are arranged on chromosomes linearly. During meiosis n Alleles locating in the same loci of the homologous will be segregated with the homologous moving to the different gametes.n The genes in the differen

5、t non-homologous are independently assorted.n The genes in the same chromosomes are linked, which will move together. n The non-alleles in the pair of the homologous might be recombined due to the cross-over occurring between the homologous. 第三部分The principle of segregationn A physical characteristi

6、c of a organism is determined by a pair of genetic factors, which is either dominant or recessive.n The pair of factors segregate from each other during the gamete formation.The principle of independent assortmentThe factors determined for different characteristics will be independently assorted dur

7、ing the gamete formation Principle of linkage and crossoverA group of genes are arranged on a chromosome linearly. They will move together with the chromosome and might be recombined due to the cross-over occurring between the pair of homologous chromosomes during meiosis.第四部分Genetic disorder or inh

8、erited disease: The diseases caused by human chromosomal aberration or DNA mutationChromosome disorders Duplication or deletion of the certain chromosomes or the certain chromosomal segments Number abnormality Structure abnormalitySingle-gene disorder Caused by single gene mutationn Mendel diseasen

9、Transferred in pedigreen Autosomal or sex chromosomaln Dominant or recessiveMitochondrial genetic disordern The mutation is in the encoding regions of mitochondrial DNAn Single gene mutationn Transmit with mitochondrial DNA - Maternal transmittingPolygenic disorderResulting from complex functions of

10、 both multiple genes and multiple environmental factorsn Family history, but incidence is much lower than Mendels modelSomatic cell genetic disordern Accumulating results of changes of multiple genes and environmental factors in a certain duration. n Mutations normally limited in somatic cellsn Muta

11、tion transmitted by mitosisChapter 2 基因Gene: a DNA segment,a basic unit of heredityn Chemically: A specific DNA segment, containing the code for the amino acid sequence of of a polypeptide chain. n In physics: Arranged on chromosome linearly, can be exchanged and transmitted to the next generation.

12、n Functionally: Controlling the expression of specific characteristics of a living organism. PromoterDNA sequences clustered around start site of transcription (5 region) specifically recognized by RNA polymerase and promoting the gene transcriptionEnhancer Promoter-specific- Tissue-specificn A DNA

13、sequence enhancing the promoter functionn Located in either upstream or downstream of start site, 3Kb or moren Both 53or 35dirctions n Function on both the genes in upstream and downstream. Terminatorn The end of downstream of genen Terminate the transcription of RNAn Composed of a reversed repetiti

14、ve sequence and specific 5-AATAAA-3Gene FusionTwo different genes are fused resulted from recombination of DNA fragmentsGenomen Total genetic information in a living organism.n Total genes in a haploidy set of chromosomes with the mitochondrial DNA.Structural geneGenes directing the synthesizing pro

15、teinsChapter 3 染色體n Chromatin is the basic components in the cell nucleusn Composed of DNA, histone and non-histone proteinn Euchromatin: Slightly and evenly stained, non- or low-repetitive DNA regionsn Heterochromatin: Darkly and unevenly stained, highly repetitive DNA regionsFluorescence In Situ H

16、ybridization（FISH）n Using DNA probe labeled with a certain markern Hybridizing with DNA in chromosomes and nuclei on slidesn Probes hybridized with the fragment in chromosome are detected by signals from the labeled markersn （Rapid mapping of genes and sequences in chromosomen Detecting small fragme

17、nt in interphase.n Detecting cryptic rearrangements or small deletions Banding could not be detected 2 relatively common alleles Genotype: the set of alleles Phenotype: the observable expression of a genotype Homozygote: a individual with identical alleles Heterozygote: a individual with different a

18、lleles Hemizygote: a individual with an allele on X chromosome, but no corresponding loci on the Y chromosome. Pedigree: A simplified diagram of a familys genealogy that shows family members relationships to each other and how a particular trait or disease has been inherited. Proband: The family mem

19、ber who first bring a family to the attention of an investigator is proband Carrier: a person who has a recessive mutated gene, together with its normal allele. Carriers do not usually develop disease but can pass the mutated gene on to their children. Pleiotropy（多效性）: one gene, more than one effect

20、 Genetic heterogeneity異質(zhì)性: the same phenotypic changes resulted from different mutations at the same locus(allelic ) or mutation at the different loci(locus ) Expressivity（表現(xiàn)度）: the severity of phenotype expression Penetrance（外顯率）: the probability of a gene expression Consanguineous marriage （近親婚配）:

21、 couple with common one or more ancestor Genetic imprinting（基因印記）: a gene expression depends on whether the allele has been inherited from the father or from the mother Anticipation（遺傳早現(xiàn)）：increasing severity or decreasing onset age of the genetic disorders in successive generationsOther factors affe

22、cting pedigree patterns Onset age Pleiotropy: one gene, more than one effect Genetic heterogeneity Expressivity and penetrance Coefficient of relationship and consanguineous marriage Sex-limited phenotypes and sex-influenced phenotypes genetic imprinting Anticipation X inactivationAutosomal Dominant

23、n The trait appears in every generation n Any child of an affected person has a 50 percent risk of inheriting the trait. n Unaffected family members do not transmit the trait to their childrenn The occurrence and transmission of the trait are not influenced by sexAutosomal Recessive The trait charac

24、teristically appears only in sibs, not in their parents. Offspring or other relatives. On the average, one fourth of the sibs of the proband are affected; in other words. The recurrence risk is one in four for each birth. The parents of affected child may be consanguineous. Males and females are equ

25、ally likely to be affected. There are many small groups in which the frequency of certain rare recessive genes is quite different from that in the general population.X-linked Recessive - The trait is passed from an affected man through all his daughters to, on the average, half their sons. The incid

26、ence of the trait is much higher in males than in females. The trait is never transmitted directly from father to son. The trait may be transmitted through a series of carrier females; if so, the affected males in a kindred are related to one another through females. Carriers show variable expressio

27、n of the trait. X-linked dominant inheritance n Affected males have no normal daughters and no affected sons.n Affected heterozygous females transmit the condition to half their children of either sex.n Affected females are more common than affected males, but as they are almost always heterozygotes

28、 they usually have milder (but Variable) expression. Y-linked Disordersthey are always passed from father to son, and they never appear in females Chapter 5 多基因病 Qualitative trait (discrete trait): A genetic disease trait that either present or absent Monogenic disease, Blood types Quantitative trai

29、t (continued variation ): are measurable characteristics such as height, blood pressure, serum cholesterol, and body mass index Characteristics of Inheritance of Complex Diseases Not single-gene disorders and do not demonstrate a simple Mendelian pattern of inheritance Demonstrate familial aggregati

30、on, because relatives of an affected individual are not likely to have disease-predisposing alleles in common with the affected person than are unrelated individuals Pairs of relatives who share disease-predisposing（疾病傾向的）genotypes at relevant（相關(guān)）loci may still be discordant（不一致）for phenotype (show

31、lack of penetrance) because of the crucial(至關(guān)緊要的) role of nongenetic factors in disease causation(原因). The most extreme examples of lack of penetrance despite identical genotypes are discordant monozygotic twins (MZ) The disease is more common among the close relatives of the proband and becomes les

32、s common in relatives who are less closely related. Greater concordance for disease is expected among MZ versus dizygotic twins (DZ) Lod score ：A measure of the likelihood of genetic linkage between loci. HapMap: A set of haplotypes, defined by tag SNPs, distributed throughout the genome, used for a

33、ssociation studies.Linkage disequilibrium (LD)(連鎖不平衡)：The occurrence together of 2 or more alleles at closely linked loci more frequently than would be expected by chance.Linkage Analysis is more difficult in multifactoral conditions than in single-gene disorders:A,Variants in more than 1 gene are l

34、ikely to contribute to the disorderB,The number of affected persons within a family is likely to be fewer than for a single-gene disordersC,The mode of inheritance is usually uncertainD,Some multifactorial disorders are likely to have more than 1 etiology(病因，病源)E,Many multifactorial conditions have

35、a late age of onsetChapter 6 群體遺傳學(xué)Mendelian populationAn interbreeding population of sexually reproducing individuals sharing a common gene pool. Gene pool : the genetic constitution of a population of a given organism.(All the genes of all the individuals in population make up the gene pool.) Genot

36、ypes: the genetic constitution of a single individual. Gene frequency (allelic frequency): the frequencies of the members of a pair of allele genes in a population. Phenotype frequencyHardy Weinberg EquilibriumStates the relationships between the frequency of alleles at a locus, and the genotypes re

37、sulting from these alleles.Hardy-Weinberg equilibrium implies that gene and genotype frequencies are constant from generation to generation. If disequilibrium occurs, equilibrium will be reestablished after one generation of random mating. H-W law rests on several assumptions:1. large population2. r

38、andom mating3. no mutations4. no migration between populations 5. no selection - all genotypes reproduce with equal successExceptions to Hardy Weinberg AssumptionsA Migration introduction / loss of allelesB Mutations may occur at different frequency in different populationsC Small population size- g

39、enetic isolate / founder effectD Non-random mating 1- consanguinity 2-assortative mating(=non-random mating)Hardy-Weinberg equilibrium law If two alleles at a gene - A and a 1. frequency of the A allele = p 2. frequency of the a allele = q3. The two fractions add up to totality p + q = l 4. the prop

40、ortions of the three genotypes: AA, Aa and aa are p2: 2pq : q25. Hardy-Weinberg formula: p2 (AA) + 2pq (Aa) + q2 (aa) = 1Changes in Allele Frequency Can be caused by: mutation (source of genetic variation) selection (phenotypes differ in biological fitness) (deleterious mutations may be removed by e

41、arly death / lack of reproduction) migration (movement in or out) F(Fitness) - the ability to contribute to the gene pool of the next generationS(selective coefficient)Heterozygote Advantage eg. Sickle cell anemia. Mutant allele has a high frequency despite reduced fitness in affected individuals. H

42、eterozygote has increased fitness over both homozygous genotypes Genetic DriftFluctuation in allele frequency due to chance in a small population.Founder Effect if an original member of a sub-population has a rare allele, it may become common in the sub-population (high carrier frequency), resulting

43、 in high frequency of rare disease.Consanguinity/Inbreeding when an individuals parents have one or more common ancestors, identifiable from a pedigree (or archival records) - because of genetic isolate, cultural practice, assortative mating -Increased likelihood of q 2Chapter 7 線粒體基因遺傳 Mitochondria

44、l genome+Small (16.5 kb) circular DNA +1 gene/0.45 kb +Very few repeats+Heavy and Light strands +No introns +93% coding Special features of mitochondrial genetics +Maternal Inhertance +Heteroplasmy +Replicative Segregation +Threshold Expression +High Mutation RateHomoplasmy & Heteroplasmy Homoplasmy

45、: The presence of only one type of mtDNA in the mitochondria of a single individual. Heteroplasmy: The presence of more than one type of mtDNA in the mitochondria of a single individual.Chapter 8 生化和分子遺傳病Homeostasisis the property of either an open system or a closed system, especially a living orga

46、nism, which regulates its internal environment so as to maintain a stable, constant condition.Molecular DiseaseA disease in which there is an abnormality in or a deficiency of a particular molecule, such as hemoglobin in sickle cell anemia. The Effect of Mutation on Pr Function1. Loss of Pr function

47、 (the great majority)2. Gain of function 3. Novel property (infrequent)4. The expression of a gene at the wrong time (Heterochronic expression), or in the wrong place (Ectopic expression), or both. (uncommon, except in cancer)Gene clusterA group of adjacent genes that are identical or related.Pseudo

48、geneDNA sequence homologous with a known gene but is non-functional.Genetic disorders of hemoglobinTwo broad groups structural variants: alter the globin polypeptide without affecting its rate of synthesis thalassemias: reduced rate of production of one or more globin chainsThalassemias can arise in

49、 the following ways:1.One or more of the genes coding for hemoglobin chains is deleted.2. A nonsense mutation that produces a shortened chain. 3. A frameshift mutation that produces a nonfunctional chain.4. A mutation may have occurred outside the coding regions.Inborn Error of MetabolismAny of a gr

50、oup of congenital disorders caused by an inherited defect in a single specific enzyme that results in a disruption or abnormality in a specific metabolic pathway.Chapter 9 免疫遺傳HaplotypeA group of alleles in coupling at closely linked loci, usually inherited as a unit.The ABO Blood Groups: 9q34 血型為A，則有A抗原，B抗體 The Rh System dd: are Rh-negative and do not have the Rh antigen. 陰性，不凝集者DD or Dd genotype: have the Rh antigen on their erythrocytes and are Rh-positive. 陽(yáng)性Hemolytic diseases of the newborn(新生兒溶血癥) Maternal-fetal Rh incompatibility (Rh-negat