遗传 three.docx

1、遗传 three遗传 3KaryotypeThe chromosome constitution of an individual.Female: 46,XX; Male: 46,XYA karyotype is described by first listing the number of chromosomes followed by the sex chromosome constitution, followed by any abnormalities in number or morphology of chromosomes.Robertsonian translocation

2、A translocation between two acrocentric chromosomes with loss of satellite material from their short arms.Marker chromosome (mar)A small chromosomal fragment the specific identity of which cannot be determined by conventional cytogenetic techniques.Chromosome BandingG-banding most widely used, tryps

3、in + GiemsaQ-banding quinacrineR-banding reverse to G-banding, saline buffer + GiemsaC-banding centromeresN-banding silver NOR stain, NOR activityThe dark-staining G-bands contain DNA that is AT-rich and are thought to contain fewer active genes.The DNA is in a condensed state in interphase nuclei a

4、nd is rich in LINES.The weakly staining bands, or R-bands, contain DNA that is GC-rich and contains many transcribed genes.The DNA is in a more extended state in interphase nuclei and contains in addition to transcribed genes, increased numbers of SINES.A karyotype is described by first listing the

5、number of chromosomes followed by the sex chromosome constitution, followed by any abnormalities in number or morphology of chromosomes.Eg：47,XY,+21 An XY male with 47 chromosomes, including an extra copy of chromosome 21, which causes Down syndrome.45,XY,der(14;21)(q10;q10) An XY male with 45 chrom

6、osomes, in whom one normal 14 and one normal chromosome 21 have been replaced by a derivative chromosome arising from the translocation of the long arm of chromosome 21 to the long arm of chromosome 14.Fluorescence In Situ Hybridization (FISH) Single-stranded probes may be hybridized to metaphase ch

7、romosomes (standard), but also can be hybridized directly to immobilized interphase nuclei of nondividing cells. Centromeric probes, telomeric probes, locus-specific probes, and whole chromosome paint probes.High-resolution “Fiber FISH”.Comparative Genomic Hybridization (CGH) - tumorN the number of

8、chromosomes in a normal haploid gameteDiploid or 2N the number of chromosomes in a normal somatic cellsEuploid any exact multiple of NPolyploidy triploidy (69 chromosomes) and tetraploidy (92 chromosomes)AneuploidFor constitutional chromosome disorders, usually refers to an extra copy of a single ch

9、romosome trisomy (as in trisomy 21 Down syndrome), or the absence of a single chromosome monosomy (as in 45,X Turner syndrome)Is the result of nondisjunction, or failure of chromosomes to separate normal during cell division, and can occur during meiosis or mitosis.Structural AbnormalitiesOnly one c

10、hromosome is involvedA deletion or duplication of a portion of the chromosomeA pericentric (involving the centromere) or paracentric (not involving the centromere) inversionFormation of a ring chromosome or isochromosomeDeletion (del) Duplication (dup) Inversion (inv) Ring chromosome (r)Isochromosom

11、e (i)Insertion (ins)Translocation (t)The chromosomal basis of Down SyndromeTrisomy 21Unbalanced translocationMosaic for a trisomy 21 cell line一个三体21细胞系的嵌合体Lyon hypothesisOne X chromosome in each somatic cell of the female is inactivated; X inactivation occurs early in embryonic life;The inactivation

12、 is random;X inactivation is complete;X inactivation is permanent.The chromosomal basis of Turner SyndromeMonosomy X (45, X)Structural abnormalitiesMosaic for a 45,X cell lineclinical consequence of constitutional chromosomal abnormalities.1：Spontaneous Abortions自发流产2：Birth Defects 出生缺陷the general f

13、eatures are a triad of growth retardation, mental retardation, and specific somatic abnormalities.生长迟缓、智力迟钝和特殊的躯体异常。Autosomal chromosome disorders (Down syndrome, Edwards syndrome, Patau syndrome, Cri du Chat syndromeDown SyndromeTrisomy 21The most common and best known of the chromosome disorders a

14、nd is the single most common genetic cause of moderate intellectual disability Approximately 1 in 850 live birthsGrowth retardation and varying degree of mental retardationClinical FeaturesBabies are often very floppy or hypotonicFacial featuresNasal bridge flat Eyes upslanting palpebral fissures, a

15、nd epicanthal foldsEars small and low-set, a characteristic folded appearanceMouth open, showing a protruding tongueBrachycephaly with a flat occiputNeck short, with loose skin on the napeHands short and board, often with a single transverse palmar crease and clinodactyly.Feet wide gap between first

16、 and second toesIQ score ranging from 25 to 75 Average IQ of young adult is around 40 to 4540% have significant congenital heart disease (often atrioventricular canal defects)5% have serious gastrointestinal anomalies, including duodenal stenosis15- to 20-fold increased risk of leukemiaPatients deve

17、lop Alzheimers disease early in life.Trisomy 18 (Edwards syndrome)Small and low-set ears, a short sternumClenched fist with overlapping fingers“Rocker-bottom” feetTrisomy 13 (Patau syndrome)Cleft lip and cleft palatePolydactylyCri du chat SyndromeApproximately 1 in 15,000 live births.Deletion of par

18、t of chromosome 5p.Crying infants with this disorder sound like a mewing cat.Disorders of Sex ChromosomeX-chromosome inactivation Lyon hypothesisTurner syndromeKlinefelter syndromeXYY syndromeXXX syndromeFragile X syndromeXYY Syndrome47,XYYApproximately 1/1000 malesTend to be taller than average.XYY

19、 males are not inclined to commit violent crimes.Increased incidence of minor behavioral disorders, such as hyperactivity, attention deficit disorder, and learning disabilities.XXX Syndrome47,XXXApproximately 1/1000 femalesOvert physical abnormalities are rarely seen, but these females sometimes hav

20、e sterility, menstrual irregularity, or mild cognitive disability.Approximately 90% of cases are the result of conjunction in the mother.Fragile X SyndromeWhen peripheral blood lymphocyte cultures are deprived of folate, or thymidine metabolism is perturbed, apparent breaks or gaps in chromosomes, s

21、o-called fragile sites, can be observes.Using these techniques, a folate-sensitive fragile site was describe at Xq27.3 in males affected with a form of X-linked mental retardation that came to be known as the fragile X syndrome.the fragile X syndrome is the most common inherited form of mental retar

22、dation in humans.Facial abnormalities, including a narrow face with prominent forehead, jaw, and ears, macroorchidism (large testes) in 90% of postpubertal affected males, mild connective tissue abnormalities, and most importantly, moderate to severe mental retardation.LocusA specific position or lo

23、cation on a chromosome.Alleles Alternative forms of a gene, or of a DNA sequence, at a given locus.Compound heterozygoteAn individual with two different mutant alleles at a given locus.Double heterozygoteAn individual with one mutant allele at each of two different loci.PedigreeA chart or diagram of

24、 an individuals ancestor used in genetics in the analysis of inheritance of specific traits.The proband The first affected family member coming to medical attention.Co-dominanceTwo allelic traits that are both expressed in the heterozygous state.Human ABO blood groupPenetranceThe proportion of oblig

25、ate gene carriers for a mutant allele who express the phenotype.ExpressivityThe nature and severity of the phenotype.Delayed onsetnot present at birth but have manifestations only later in life.Polycystic kidney diseaseHuntington diseaseGenomic imprintingThe differential expression of alleles depend

26、ing on the parent of origin.Eg:染色体15q11-q13父源缺失：Prader-Willi Syndrome (PWS)母源缺失：angelman综合征ASAnticipationAn earlier age of onset and increasing severity in successive generations.eg：Myotonic dystrophy肌强直性营养不良The most common muscular dystrophy affecting adults.Muscle wasting, beginning in the face (a

27、nd causing the characteristic mask like facies with ptosis or drooping eyelids), neck, and hands, but gradually becoming generalized.Myotonia, or the inability of a muscle to relax after contraction.分子基础为动态突变CarriersHeterozygous individuals who are clinically normal but heterozygous for the mutant a

28、llele.Genetic heterogeneityDifferent mutations can cause an identical or similar phenotype.HemizygousX-linked genes are fully expressed in males, who have only a single X chromosome Functional cloningGene cloning approach moving from the basic biochemical defect to the responsible gene.Positional cl

29、oning To locate the gene responsible for a human disease based solely on its map position, without the benefit of any functional information.Holandric inheritanceThe pattern of inheritance of genes on the Y chromosome; only males are affected and the trait is transmitted by affected males to their s

30、ons but to none of their daughters. Typical pedigree pattern for AD1. Vertical inheritance.2. Both males and females are affected with equal probability.3. Each affected individual has one affected parent.4. On average, half of the offspring of an affected parent being affected, but none of the offs

31、pring of unaffected parent.Typical pedigree pattern for AR1The characteristic pedigree pattern is horizontal.2Males and females are affected with equal probability.3The usual mating is that between two carriers, and there is a 1 in 4 chance that each offspring will affected.Typical pedigree pattern

32、for XR1. Only males are affected.2. The disease is transmitted by healthy female (heterozygous carriers).3. The disease can be traced among male relatives on the mothers side of the family.Characteristic of mtDNA(简答题）Semi-autonomous，Genetic code variants，Maternal inheritance，Replicative segregation，