Chromosomal Abberations Numbers (PDF)

Variations in chromosome number and arrangement Large scale chromosomal changes Concept of genetics 9th edition Chapter 8. p199  Sources of Genomic Variations  Alleles– arises through gene mutations. Never detected microscopically  Crossing...

Variations in chromosome number and arrangement Large scale chromosomal changes Concept of genetics 9th edition Chapter 8. p199  Sources of Genomic Variations  Alleles– arises through gene mutations. Never detected microscopically  Crossing over---recombination.  Independent assortment.  Chromosomal mutations or aberrations. 1- Variations in chromosomes numbers. 2- Rearrangements within (same chromosome) or between chromosomes. Can be detected under the microscope  variations In plants even change in chromosome numbers can be tolerated. Sometimes re-arrangements could be tolerated in animals. Loss or gain of chromosomes are deleterious. Sex chromosomes aberrations are tolerated more than autosomes Chromosomal abnormalities causes change in gene numbers and position Chromosomal breakage if occurs within a gene functionally disrupt this gene. Chromosome mutations can be divided in 2 categories: changes in numbers, and structures.  Terminology Euploid – chromosomes present in complete haploid sets – Haploid ( monoploid) – Diploid. – More than 2 sets (Polyploid) example Triploid, Tetraploid Aneuploid – loss or gain of one or more chromosomes but not a complete set Variation in chromosome numbers – Cause: Nondisjunction Commonly results from nondisjunction during meiosis. Paired homologs fail to disjoin during segragation. The process disrupt the normal distribution of chromosomes into gametes – Monosomy, trisomy, tetrasomy, etc. – Klinefelter and Turner syndromes are examples involving human sex chromosomes  Nondisjunction. The cause of variations in chromosome numbers  Other causes- Viral infection ionization radiation and chemical toxins  Monosomy 2n – 1 condition Monosomy involving autosomes may have severe phenotypic effects in animal species (but generally not plants). – Monosomy for Drosophila chromosome 4 ( Haplo IV) (only 5% of genome) gives live fly but small and with low viability – Monosomy for chromosomes 2 and 3 lethal. – The severity of monosomy are puzzling. Still monosomy possess one copy. Think about it. – What’s about recessive lethal alleles.  Cri-du-Chat Syndrome Autosomal monosomy in humans not reported beyond birth (die quickly) Partial autosomal monosomy may survive – Segmental deletions of chromosomes “Cry of cat” syndrome – Loss of part of 5p arm (46, -5p). Most often sporadic. Not inherited. – 1/25,000-50,000 births – Cry, similar to the meowing of the cat. – Gastrointestinal and cardiac complications. – Mental retardation – abnormal development of glottis and larynx  Cri-du-Chat Effect of the syndrome is severe and depends on the deleted portion. Most individuals could achieve motor and language skills and may be home-cared.  Partial Monosomy: Cri-du-chat Syndrome (46, -5p) In 2004 it was reported that the portion of chromosome that is missing Contains the TERT gene which encodes telomerase reverse transcriptase  Telomerase adds telomeric repeats to the 3’ termini of the chromosome -only the catalytic (hTERT) and RNA (hTR) components are required for activity in vitro hTERT hTR CAAUCCCAAUC Whether the absence of this gene on one homolougue is related to the multiple phenotypes of Cri-du-chat is still unknown Trisomy in plants Figure 8.2  Down syndrome Only human autosome with significant numbers survive longer than a year after birth. 1866 first reported by John Langdon Down ( had a grandson with this condition). 1950: Down syndrome is a Result from extra copy of chromosome 21. Trisomy: Down Syndrome (47, +21) )Affect 1/800 birth ( )e.g: 5500 such births annually in US. 350,000 individual in US  Down syndrome- Phenotypic charecters Many phenotypes. (12-14). Each individual in average express 6-8 phenotypes. Flat face, round head, short status, protruding furrowed tongue, mouth partially open, palm pattern, short hands etc--- Average lifespan 50 years. Incidence of leukemia ( 20X higher than normal). Death most frequently in older down syndrome is due to Alzheimer. Prone to respiratory diseases  ,Down Syndrome  Most often occurs by nondisjunction of chr. 21 during meiosis; in theory could occur in either mom or dad, but 95% of these trisomies have defective egg as source.  Critical region in chromosome 21 contains genes that are dose sensitive  Down syndrome critical region (DSCR) have been hypothesized.  Mice model in 2004 that is trisomic for this region was created.  Some mice fail to express the characteristics.  Still a lot of work have to be done  Incidence 1/800-1000 at maternal age 30. 1/100 at maternal age 40. ( 10 fold). 1/30 at maternal age 45. Reason: Ovum age?. Late pregnancy: genetic counseling is highly recommended. Also prenatal diagnoses. Non-invasive techniques. Familial down syndrome: We will talk in other location Incidence of Down Syndrome Increases with Maternal Age All eggs are formed by birth and arrested in meiosis; is the correlation of increased age and the syndrome due to more non- disjunction in older eggs?  Trisomy 13: Patau Syndrome (47,+13). Klaus Patau. 1960 A lethal condition. Severe development malformation. 1 in 19,000 births. Average survival : 3 month. Fig. 6-16, p. 133  Other trisomies: Patau Syndrome (47, +13) 1 / 19,000 live births Edwards Syndrome (47, +18). Second most common.after Down 1 / 8000 live births  VARIATIONS ON SEX CHROMOSOME NUMBERS. Trisomy Klinefelter syndrom. (47,XXY). 1 in 1000 male births Genetilia and internal ducts are present as in males. Their testes are underdeveloped and fail to produce sperms. They have enlarged breast. Mentally retarded. Feminine sexual development is not entirely suppressed.  Turner syndrome XO. Monosomy. (45,X). 1/10,000. Short status. Under 5 feets. wide chest extra skin folds on neck underdeveloped sexual characteristics rudimentary ovaries, sterile no mental retardation is associated with this syndrome  If nondisjunction was mother b.  P: XX x XY.c  X Y XX XXX XXY Super female Klinefelter 0 X0 0Y Turner Lethal If nondisjunction was father.b P: XX x XY.c XY 0 X XXY X0 Klinefelter Turner X XXY X0 Klinefelter Turner  Dosage compensation  Female cells have double the number of X chromosomes as male cells. Therefore, female cells should express twice the amount of X chromosome genes than male cells. BUT - they DON’T.  Male and female cells express X chromosome genes at the same level.  Several ways that this might be achieved. XX XY  Dosage Compensation Mechanisms from Straub and Becker, Nature Rev.Genet. 8, 47 (2007) Genomes compensate for different numbers of sex chromosomes by adjusting gene expression levels  Inconsistencies between syndromes and X inactivation  If normal XX female has one X inactivated, why is a X Turner female not normal?  Similarly, if XXY male has one X inactivated, why does he have Klinefelter syndrome?  Perhaps not complete inactivation  Or inactivation does not happen immediately, Then some overexpression of X-linked genes The Lyon Hypothesis of X Inactivation ”Lyonization“  Proposed by Mary Lyon and Liane Russell (1961)  Which X is inactivated? Paternal or maternal?  In marsupials the parental x is inactivated  In placental mammals ( Human)-Inactivation of X chromosome occurs randomly in somatic cells during embryogenesis.  Progeny of cells all have same inactivated X chromosome as original, creating mosaic individual Lyon-Hypothesis: X-inactivation A precursor cell to all coat color cells Random inactivation early in dev. **Also in calico cats  Xist gene X Chromosome Inactivation Barr body Heterochromatin formed, genes silenced Mosaicism Reveals the Random Inactivation of one X chromosome Anhidrotic ectodermal dysplasia in a heterozygous woman Regions where sweat glands are absent.  What we know: 1. Normally occurring X-inactivation via XIST 2. Gene dosage problem – Trisomy 21  Predicting Gene Expression Aim: Investigate how formation of a Chr21 Barr body affects gene expression Method: Samples - 3 different cell types: Technique : Wild type Trisomy 21Trisomy 21 + XIST Quantify gene expression from chromosomes 9 & 21 Predict: The level of gene expression in each cell type, from the two different chromosomes. Draw your predicted gene expression data on the graph provided.  Some statistics 25% of overall pregnancies spontaneous abortion. 50% of these, show chromosomal anomaly. So 12.5% of all pregnancy originate with abnormal # of chromosomes. 90% of all chromosomal anomalies terminated by spontaneous abortion. 65% are aneuploids. Highest incidence is (45,X). More recent figures: 10-30% of all fertilized eggs in human contain some errors.  Polyploidy- 2 ways Generation If addition of one or Polyploidy is very more extra sets of common in plants chromosomes identical but rarer in animals to the normal haploid (Mostly in lizards, (autopolyploidy).  If different speceis amphibians and fish) ( Hybrid), Even numbers of sets allopolyploidy. generally more stable and therefore more common Polyploid Terminology and Modes of formation  Inferring the genomic Composition of Polyploids  Examples of plants with polyploid genomes: Allopolyploidy Autopolyploidy  Allopolyploids Allopolyploids form only between closely related species; however, the different chromosome sets are only homeologous (partly homologous), not fully homologous as they are in autopolyploids.  Polyploid and size There is often a correlation between the number of copies of the chromosome set and the size of the organism. A tetraploid organism, typically looks very similar to its diploid counterpart in its proportions, except that the tetraploid is bigger, both as a whole and in its component parts. The higher the ploidy level, the larger the size of the organism  Autopolyploidy Applications Treating a plant with colchicine often produces autopolyploidy, resulting in plants with larger flowers and/or fruit, 4n 2n 8n 2n  Autopolyploidy Each additional set of chromosomes is identical to the parent species Origin – Complete failure to segregate during meiosis (first or second division nondisjunction) – Multiple sperm fertilize an egg Experimentally produced by cold or heat shock during meiosis or by colchicine  Colchicine Treatment Cells undergo S-phase, no separation of chromosomes is accomplished, no cell division occurs, at Telophase, the nuclear membrane reforms, treatment for one cell cycle leads to 4n cells.  Endopolyploidy Only certain cells of an otherwise diploid organism are polyploid – Some human liver cells are 4n, 8n or 16n – Some apical region tissues of plant – Gut lining of mosquitoes can be 16n – Some tissues of insects in genus Gerris (water strider) Up to 2048 copies of genome (2n = 22 so some cells have 40,000+ chromosomes)  Triploid creation 4n x 2n = 3n? The creation of triploids can be accomplished by crossing a tetraploid with a diploid, Most triploid individuals are sterile. Meiotic pairing in triploid  homologs (bivalents) segregate to opposite poles, but the unpaired homologs (univalents) pass to either pole randomly. In a trivalent, a paired group of three, the paired centromeres segregate as a bivalent and the unpaired one as a univalent.  Monoploid Monoploids Male bees, wasps, and ants are monoploid. In the normal life cycles of these insects, males develop by parthenogenesis (the development of a specialized type of unfertilized egg into an embryo without the need for fertilization). In most other species, however, monoploid zygotes fail to develop. The reason is that virtually all members of a diploid species carry a number of deleterious recessive mutations, together called a genetic load.  Abnormality of Monoploids monoploids are characteristically sterile. (Male bees, wasps, and ants bypass meiosis; in these groups, gametes are produced by mitosis.) Monoploids that do develop to advanced stages are abnormal. If they survive to adulthood, their germ cells cannot proceed through meiosis normally, because the chromosomes have no pairing partners.  Monoploid Applications Screening for favorable traits monoploid plants can be created by culturing pollen grains (n = 1), – the population of haploid organisms is then screened for favorable traits – the plants are then treated with colchicine which generates a 2n plant homozygous for the favorable traits.