Chromosomes

Chromosome• Tightly coiled DNA form • Found during mitosis and

meiosis• Made mostly of DNA and

proteins• Centromere- point of

attachment• Chromatids- each arm of a

chromosome in replicated form

• Banding▫ Heterochromatin- dark

area with repetitive sequences

▫ Euchromatin- lighter protein-encoding area

Chromosome Structure: Telomeres

• Chromosomal tips

• Human chromosomes have repeats of TTAGGG

• Telomeres shorten during each cell division in most cells

Chromosome Structure: Centromere• Constricted region of

chromosome• Region of attachment of

spindle fibers during mitosis and meiosis

• Contains many repeats of a 171-base sequence called the alpha satellite

• Centromere associated proteins▫ Some form kinetochore

during mitosis and meiosis▫ Centromere protein A

(CENP-A)- surround centromere; are divided and continue with each chromatid during anaphase

Chromosome Structure• Moving away from the centromere

▫ Gene-rich regions▫ Subtelomeres

Gene start to taper off More repeats start to occur

Chromosome Shorthand• Shorthand used to locate

gene on chromosome• First number is

chromosome number• Letter (p or q) refers to

the arm• Second number refers to

the band on that arm▫ Number gets higher as

the band is farther from the centromere

Chromosomal Differences•Size Difference

▫Chromosomes are numbered from 1 (largest)-22 (smallest)

•Banding differences•# of Genes

▫Some chromosome have very few genes for their size, and some have a lot of genes for their size

•Location of Centromere

Location of the Centromere• Metacentric- located in the

middle; divides chromosomes into two equal arms

• Submetacentric- located slightly off of center; divides the chromosome into a long (q) arm and a short (p) arm

• Acrocentric- located near one end of the chromosome; divides the chromosome into a long (q) arm and a chort (p) arm

• Telocentric- located at the end; humans do not have these

Karyotype• Pictorial representation of

chromosomes• Autosomal chromosomes

are lined up by number (from largest to smallest)

• Sex Chromosomes are arranged last

• What does it tell you?▫ Sex of individual▫ Presence of chromosomal

abnormality

Obtaining a Sample• Blood sample or cheek cell

sample• Embryo

▫ Amniocentesis▫ Chorionic Villus Sampling▫ Fetal Cell Sorting▫ Pre-implantation Testing

Creating a Karyotype•Cell division is stopped with colchicine•Cell is ruptured•Cell with the most spread out chromosomes is

used•Chromosomes are identified with stain or FISH

▫Staining- use chromosome specific stains▫FISH (fluorescence in situ hybridization)-

fluorescent probes are attached to chromosomes; each chromosome fluoresces a different color

Karyotype Analysis Shorthand• 46,XX• First number- number of

chromosomes• Sex chromosomes• Extra information

▫ Extra chromosomes (+#)

Chromosomal Abnormality: Polyploidy• Extra set of chromosomes• Triploid (3 sets)

▫ Ovum is fertilized with two sperm

▫ One gamete remains diploid after meiosis

• Usually spontaneous abortion

Chromosomal Abnormailty: Aneuploidy• Have a missing or extra

chromosome• Most are spontaneously

aborted• Some types can survive

until birth• Monosomy- missing one

chromosome▫ Only one viable is XO

(Turner Syndrome)• Trisomy- extra

chromosome

Nondisjunction• Most aneuploidy results

from nondisjunction• Chromosomes fail to

separate during meiosis• More commonly seen in

females (especially with older maternal age)

• Results in some gametes missing chromosomes and some having extra

Mosaics• Aneuploidy occurs

during mitosis• Individual has some

cells that are normal and some that are aneuploid

• Severity of disorder depends on when during development that it happens

Common Aneuploids•Autosomal

▫47, X__ +21– Down Syndrome▫47, X__ +13- Patau Syndrome▫47, X__ +18- Edward Syndrome

•Sex Chromosome▫45, XO- Turner Syndrome▫47, XXX- triplo-X▫47, XXY- Klinefelter’s Syndrome▫47,XYY- Jacobs Syndrome

Chromosomal Alterations•Structural problems of chromosomes•Include

▫Deletions▫Duplications▫Translocations▫Inversions

Deletions• Deletion of part of a

chromosome• The larger the deletion,

the more severe the disorder

• Microdeletions- small deletions that can create symptoms (ex: impair fertility if on Y chromosome)

• Cri-du-chat- deletion of part of the short arm of chromosome 5 (5p-)

Duplication• Chromosome with

repeated sections• Usually repeats have

to be large to be symptomatic

• Fragile X syndrome- expanding triplet repeat adds extra material to X

Translocations• Two nonhomologous chromosomes exchange or

combine parts• Robertsonian translocation- short arms are

removed from two chromosomes; long arms stick together to form one long chromsome▫ Problems for future generations

• Reciprocal translocation- two different chromosomes exchange parts▫ Problem for individual if gene is broken▫ Problem for future generations

• Translocation carrier- asymptomatic carrier of translocation

Robertsonian Translocation

Reciprocal Translocation

Inversion• Chromosome with some genes inverted• Paracentric inversion-

▫ Does not include centromere▫ Crossing over can result in

Normal chromosomes Dicentric chromosome (two centromeres) Acentric chromosome (no centromere)

• Pericentric inversion-▫ Does include centromere▫ Crossing over can result in▫ Normal chromosomes▫ Abnormal chromosomes with one centromere

Inversion

Isochromosomes and Ring Chromosomes• Isochromosome

▫ Chromosome splits the wrong way during meiosis

▫ Chromosome end up with identical arms

• Ring Chromosome▫ Removal of telomeres

creates sticky end ▫ Sticky ends attach to

each other creating a ring

Uniparental Disomy•Individual has a chromosome set where

both chromosomes come from one parent •Can cause problems with recessive alleles

or imprinting•Occurs if

▫One parent has nondisjunction resulting in a gamete with that chromosome missing

▫One parent has nondisjunction resulting in a gamete with both homologs of that chromosome

▫These two fertilize each other