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Chromosome Mutations

Fundamental GeneticsLecture 7

John Donnie A. Ramos, Ph.D. Dept. of Biological Sciences

College of Science University of Santo Tomas

Chromosome Mutations

Also called chromosome aberrations

Change in number of chromosomes, deletion or duplication of genes or segments of chromosome, or rearrangement of genetic material

Inherited (can be passed from one generation to another)

Results to new phenotypic variation or maybe lethal

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Variation in Chromosome Number

NondisjunctionFailure of homologous chromosomes to segregate during anaphase of meiosisPrimary nondisjunction – failure of a homolog to segregation during anaphase ISecondary nondisjunction – failure of a homolog to segregate during anaphase IIResults to aneuploidy

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Monosomy

Loss of one chromosome (2n-1)

Caused by either primary or secondary nondisjunction

Human Example: Turner syndrome (2n=45, 44+X)

Monosomy involving autosomes in humans is lethal

Drosophila Example: Haplo IV (monosomic at chromosome no. 4)

Slow development, reduced body size, impaired viability

Common in plants (maize, tobacco, primrose) – less viable compare normal plants

Cri-du-Chat Syndrome

Cri-du-Chat syndrome (cry of cat)Deletion in part of chromosome 5 (46, 5p_)Gastrointestinal and cardiac complicationsMentally retardedAbnormal development of glottis and larynx (cry like a cat)Incidence: 1 in 50,000 birthsDifferent cases have different degrees of truncations

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TrisomyGain of chromosome (2n+1)Caused by either primary or secondary nondisjunctionAffected are viable in humans, animals and plantsExample: Trisomy 21 (Down Syndrome)

Trisomy of chromosome 21 (2n=47, 21+)1 in every 800 live birthsFlat faces, round heads, protruding and furrowed tongues, short and broad fingersPhysical, psychomotor, and mental development is retardedLife expectancy: 50 yrs old95 % of cases are nondisjunction in ovum (related to age of female)

Trisomy

Patau Syndrome

(Tisomy 13)

2n= 47, 13+

Edwards Syndrome

(Trisomy 18)

2n = 47, 18+

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PolyploidsPresence of more than two sets of chromosomes

Infrequent in many animals species but common in amphibians, lizards and fishes

Very common in plant species

Same species Different species (hybridization)

AutopolyploidsTriploid (AAA), tetraploid (AAAA), pentaploid (AAAAA) if A represents haploid setArise as a result of: (for triploids)

Failure of all chromosomes to segragateTwo sperm fertilizing an eggExperimentally induced (diploid x tetraploid)

Autotetraploids are more likely to occur in nature than autotriploids (because of genetically unbalanced gametes)Tetraploids result when chromosomes replicated but sister chromatids failed to divideExamples: potatoes, seedless watermelon, commercial bananas, apples, peanuts, coffee, strawberry (octaploid)

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Allopolyploids

Hybridization of two closely related species

Allotretraploid – 4 sets of chromosomes (Two sets from species 1 and two sets from species 2)

Amphidiploid – the resulting hybrid from2 species

Ex. American cotton (2n=26);

Raphanus brassica (2n=18) = Raphanus sativus (radish) + Brassica olaracea (cabbage)

Triticale = rye (high lysine) and wheat (high protein)

Variation in Chromosome Number

Structural changes in a particular chromosome

Deletions, duplications or rearrangements of genes

Caused by chromosomal breaks (mutations) –spontaneous or artificial (due to mutagenic agents)

Heritable

Can change the phenotype of an organism

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Deletions

Lost of a gene or a part of gene

Either terminal or intercalary deletions

When a chromosome has intercalary deletion, its homolog will undergo compensation loopduring pairing of homologous chromosomes.

Example: Cri-du-ChatSyndrome

DuplicationsA gene locus or apiece of chromosome is present more than once in a genome

Result of unequal crossing-over during meiosis

Can form compensation loop in succeeding homologous pairing

Causes gene redundancy and amplification (ex. Genes coding for rRNA – E. coli has 5-10 copies but oocyte has 400 copies)

Plays a role in evolution of genes (ex. Trypsin and chymotrypsingenes; myoglobin and hemoglobin genes; myosin and paramyosingenes)

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DuplicationsCan cause phenotypic variation

Ex. Bar eye mutation in Drosophila (slit-like eyes)

Identified in 1920s by Alfred Sturtevant and Thomas Morgan

Duplication in region 16A of X chromosome

Normal Wild-type

Heterozygous

Homozygous recessive

Double bar

InversionsOccurs when a region of chromosome is turned 180°

Chromosome part is not lost but rearrangement of genes occur

Two breaks occur

Types:

Paracentric Inversion – centromers is not a part of the inverted sequence

Pericentric Inversion – centromere is part of the inverted sequence

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Paracentric Inversion Heterozygotes

Only 1 homolog is inverted

Forms inversion loop during meiosis

If no crossing-over: results to 2 normal sequence and 2 inverted sequences

If crossing occurs: results to 4 different sequence combinations

Acentric chromosome may be lost during anaphase

Pericentric Inversion Heterozygotes

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TranslocationsTransfer of chromosome segment to another location (different chromosome)Reciprocal translocation – exchange of segments between two non-homologous chromosomesResults to partial monosomy or trisomy

Translocations in Humans

Familial Down Syndrome14/21 D/GRobertsoniantranslocation (transfer of large segment of chrom. 21 to chrom. 14)

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Fragile Sites in Humans

Regions in chromosomes susceptible to DNA breakageResult of short sequence duplicationsExamples:Fragile X Syndrome (Martin-Bell Syndrome)

Presence of Folate-sensitive site on X chromosomeMost common form of mental retardationAffects 1 in 1250 males and 1 in 1500 femalesA dominant trait (but not fully expressed – only 30% and 80% of females and males with fragile X express the disease, respectively)Long, narrow faces; enlarge ears; increased testicular sizeCaused by FMR-1 gene – (trinucleotide repeats- CGG repeats)Normal persons = 6-54 repeats; carriers =55-200 repeats; fagile X= more than 200 repeats)Undergoes Genetic Anticipation –repeats increase in succeeding generations

Fragile Sites and CancerLung, stomach, esophagus, colon cancersCaused by FHIT gene (Fragile histidine triad) located in chromosome 3