CHROMOSOMES MUTAIONS

PLAN OF LECTURE1. MUTATION AND ITS TYPES.2. CHROMOSOMAL ABERRATIONS: 1)DELETION; 2) DUPLICATION; 3)

INVERSION; 4) TRANSLOCATION. 3. GENOMIC MUTATION (CHROMOSOME

MUTATION): 1) POLYPLOIDY; 2) ANEUPLOIDY.4. AUTOSOMAL MUTATIONS.5. SEX-CHROMOSOMES MUTATIONS.

You should prepare for the practical class using the existing textbook and lecture

Applicable literature materials:Medical biology / K. L. Lasarev – Simferopol: IAD

CSMU, 2002 p.181 - 188.Key words and phrases: mutation, genomic mutation, polyploidy, aneuploidy, chromosomal aberrations, deletion, duplication, inversion, translocation, oncogene, aneuploidy (heteroploidy), euploidy (polyploidy), monosomy, trisomy, autosomal trisomic, sex-chromosome polysomy, monosomy X.

HEREDITARY

INFORMATION

LIES IN

CHROMOSOMES.

THE

EUKARYOTIC

CHROMOSOMES

ARE LOCATED

WITHIN

THE NUCLEUS OF

THE CELL.

MUTATION VARIABILITY

• MUTATION - A PERMANENT TRANSMISSIBLE CHANGE IN THE GENETIC MATERIAL, MODIFICATION IN CHROMOSOMES AND GENES. • CHROMOSOMAL MUTATIONS MAY BE THE

RESULT OF CHANGES IN THE STRUCTURE OR NUMBER OF CHROMOSOMES. • THERE ARE 2 MAIN TYPES OF

CHROMOSOMES MUTATIONS:

1.CHROMOSOMAL ABERRATIONS - CHANGES IN STRUCTURE OF CHROMOSOMES.2.GENOMIC MUTATION - CHANGES IN NUMBER OF CHROMOSOMES. CERTAIN FORMS OF CHROMOSOMAL MUTATION MAY AFFECT SEVERAL GENES AND HAVE A MORE PROFOUND EFFECT ON THE PHENOTYPE THAN GENE MUTATIONS.

CHROMOSOMAL ABERRATIONS - CHANGES IN STRUCTURE OF CHROMOSOMES

CHROMOSOMAL MUTATIONS OR ABERRATIONS

INVERSION

A SEGMENT OF A CHROMOSOME SEPARATES AND REJOINS IT IN AN INVERTED POSITION. INVERSION CHANGES THE SEQUENCE OF NITROGENOUS BASES IN THE CHROMOSOMES. INVERSION OCCURS WHEN A REGION OF A CHROMOSOME BREAKS OFF AND ROTATES THROUGH 180° BEFORE REJOINING THE CHROMOSOME.

INVERSION

NO CHANGE IN GENOTYPE OCCURS AS A RESULT OF INVERSION BUT PHENOTYPIC CHANGES MAY BE SEEN. THIS SUGGESTS THAT THE ORDER OF GENE LOCI ON THE CHROMOSOME IS IMPORTANT, A PHENOMENON KNOWN AS THE POSITION EFFECT.

TRANSLOCATION A SEGMENT OF CHROMOSOME BREAKS OFF AND JOINS A NONHOMOLOGOUS CHROMOSOME. BOTH THE AFFECTED CHROMOSOMES GET MODIFIED. THE DONOR SUFFERS DELETION AND BECOMES SHORTER THAN NORMAL. THE RECIPIENT HAS AN EXTRA SET OF GENES AND BECOMES LONGER THAN NORMAL.

RECIPROCAL TRANSLOCATION

RECIPROCAL TRANSLOCATION BETWEEN NONHOMOLOGOUS CHROMOSOMES CAN PRODUCE TWO NEW HOMOLOGOUS PAIRS OF CHROMOSOMES.

ROBERTSONIAN TRANSLOCATION ROBERTSONIAN TRANSLOCATION – SPECIAL SORT WHERE THERE IS NONRECIPROCAL EXCHANGES OF DNA, FUSION OF TWO ACROCENTRICS TO GIVE A METACENTRIC, CENTROMERIC FUSION.

ROBERTSONIAN TRANSLOCATION

IN SOME CASES OF DOWN'S SYNDROME, WHERE THE DIPLOID NUMBER IS NORMAL, THE EFFECTS ARE PRODUCED BY THE TRANSLOCATION OF AN EXTRA 21 CHROMOSOME ONTO A LARGER CHROMOSOME, USUALLY 13,14,15.

DELETION A SEGMENT OF A CHROMOSOME SEPARATES AND IS LOST. THE AFFECTED CHROMOSOME LOSES CERTAIN GENES, AND BECOMES SHORTER THAN NORMAL. IF DELETION AFFECTS THE SAME GENE LOCI ON BOTH HOMOLOGOUS CHROMOSOMES THE EFFECT IS USUALLY LETHAL.

DUPLICATION A FRAGMENT OF A CHROMOSOME JOINS A HOMOLOGOUS CHROMOSOME. THE ADDITIONAL REGION OF GENES MAY BE INCORPORATED WITHIN THE CHROMOSOME OR AT ONE END OF THE CHROMOSOME, OR BECOME ATTACHED TO ANOTHER CHROMOSOME. THESE CHANGES, IF NOT LETHAL, MAY CAUSE PROFOUND CHANGES IN THE PHENOTYPE.

CHROMOSOME ABNORMALITIES AND CANCER

TRANSLOCATIONS AND INVERSIONS CREATE NEW ARRANGEMENTS OF GENES, SOME GENES ARE MORE HIGHLY EXPRESSED OR ARE MUCH LESS EXPRESSED, THERE ARE "POSITION EFFECTS" ON GENE EXPRESSION, SOME OF THESE CHANGES LEAD TO CANCER, OVEREXPRESSION OF AN ONCOGENE OR UNDEREXPRESSION OF A TUMOR SUPPRESSOR GENE CAN LEAD TO CANCER.

CHROMOSOME ABNORMALITIES AND CANCER

GENOMIC MUTATION

CHANGES IN THE NUMBER OF CHROMOSOMES ARE USUALLY THE RESULT OF ERRORS OCCURRING DURING MEIOSIS BUT THEY CAN ALSO OCCUR DURING MITOSIS. THESE CHANGES MAY INVOLVE THE LOSS OR GAIN OF SINGLE CHROMOSOMES, A CONDITION CALLED ANEUPLOIDY OR HETEROPLOIDY.

ANEUPLOIDY - HETEROPLOIDYMONOSOMY – LOSS OF A CHROMOSOME, SO A "DIPLOID -1" , HAS ONLY ONE COPY OF A PARTICULAR CHROMOSOME RATHER THEN TWO. EXAMPLE: MONOSOMIC (2N-1), 45(X0)TRISOMY – GAIN OF A CHROMOSOME SO THERE ARE THREE OF ONE SORT/ EXAMPLE: TRISOMIC (2N+1), 47 (XXX)

SEX-CHROMOSOMES MUTATIONS

ANEUPLOIDY IS THE LOSS OR GAIN OF SINGLE CHROMOSOMES, NUMERAL CHANGES (ANEUPLOIDY) IN SEX CHROMOSOMES. SEX-CHROMOSOME POLYSOMY A. TRIPLE X: (47, XXX); TRISOMY X; FEMALE. B. DOUBLE Y: (47,XYY); TRISOMY; DISOMY Y; MALE.

C. KLINEFELTER SYNDROME; (47, XXY); TRISOMY; MALE. THESE INDIVIDUALS TEND TO BE TALL, STERILE, WITH MILD MENTAL RETARDATIOND. TURNER SYNDROME; (45, XO); MONOSOMY X; FEMALE. THESE INDIVIDUALS TEND TO BE SHORT, STERILE, WITH NORMAL MENTAL DEVELOPMENT

Sex-chromosome polysomy a. triple X: (47, XXX); trisomy X;

POLYPLOIDYTHE INCREASE IN ENTIRE HAPLOID SETS OF CHROMOSOMES, A CONDITION CALLED POLYPLOIDY.MONOPLOID CHROMOSOME SET 1N – THE BASIC CHROMOSOME SET OF A SPECIES.

POLYPLOIDY, HAVING A PERFECT, BALANCED CHROMOSOME COMPLEMENT. HUMAN TRIPLOIDS 3N=69 AND TETRAPLOIDS 4N=92 ARE NOT VIABLE. POLYPLOID HUMAN EMBRION DIE. BUT TETRAPLOID CELLS IN NORMAL MAY BE IN HUMAN LIVER.

AUTOPOLYPLOIDY

MOSAICISM

TWO TYPES OF MOSAICISM

MOSAICISM

MOSAICISM

DO YOU HAVE A QUESTIONES?

THE END