Genetics Chapter 8 and 19

Chromosome Morphology

position of centromere on the chromosomes

• metacentric (middle)

• submetracentric (near middle)

• acrocentric (near end)

• telocentric (end)

• p arm (short arm)

• q arm (long arm)

Karyotype

a visual representation of an individual's complete set of chromosomes, organized by size, shape, and number.

Banding

Staining techniques help to distinguish among chromosomes of similar size and shape.

G Bands

• Stain: Giemsa dye

• Dark Bands Are: A–T rich DNA and heterochromatin

Q Bands

• Stain: Quinacrine mustard

• Visualization: UV fluorescence

• Bright Bands: A–T rich regions

C Bands

• Stain: Alkali treatment + Giemsa

• Dark Region: Constitutive heterochromatin, especially centromeres

R Bands

• Stain: Heat treatment + Giemsa

• Shows: R bands (Reverse of G-bands)

• Dark Bands Are: C–G rich regions

• Use: Highlights gene-rich (active) chromosomal areas

Types of chromosome mutations

• Chromosome rearrangements (alter the structure of chromosomes)

• Aneuploidy (alters the number of chromosomes)

• Polyploidy (one or more complete sets of chromosomes are added)

Chromosomes rearrangments

Alter the structure of chromosomes

Four types: duplication, deletion, inversion, and translocation

Duplication

Duplication of a chromosome segment

Effects of Chromosome Duplication (1)

In an individual heterozygous for a duplication, the duplicated region loops out during pairing in prophase

Effects of Chromosomes Duplication (2)

The Bar phenotype in Drosophila melanogaster results from an X-linked duplication.

(a) Wild-type fruit flies have full-sized eyes. (b) Flies that are heterozygous and (c) homozygous for the Bar mutation have smaller, bar-shaped eyes. (d) Flies with double Bar have three copies of the duplication and much smaller bar-shaped eyes.

Effects of Chromosome Duplications (3)

Unequal crossing over produces duplications and deletions

Unbalance Gene Dosage

There are too many or too few copies of a gene, which causes the cell to make too much or too little of its protein.

Deletions

loss of a chromosomal segment

Effect of Chromosome Deletion

Large deletions can be easily detected; during the pairing of homologs in prophase I of meiosis, normal chromosome loops out

Duplication on chromosome 4, short arm

Symptoms: Small head, short neck, low hairline, reduced growth, intellectual disability.

Duplication on chromosome 4, long arm

Symptoms: Small head, sloping forehead, hand abnormalities.

Duplication on chromosome 7, long arm

Symptoms: Delayed development, head asymmetry, fuzzy scalp, small nose, low-set ears.

Duplication on chromosome 9, short arm

Symptoms: Characteristic facial features, variable intellectual disability, high/broad forehead, hand abnormalities.

Deletion on chromosome 5, short arm

Cri-du-chat syndrome 

Small head, distinctive cat-like cry, wide-set eyes, round face, intellectual disability.

Deletion on chromosome 4, short arm

Wolf–Hirschhorn syndrome
Small head with high forehead, wide nose, cleft lip/palate, severe intellectual disability.

Deletion on chromosome 4, long arm

Small head, mild–moderate intellectual disability, cleft lip/palate, hand/foot abnormalities.

Deletion on chromosome 7, long arm

Williams–Beuren syndrome

Distinct facial features, heart defects, and cognitive impairment.

Deletion on chromosome 15, long arm

Prader–Willi syndrome

Poor feeding early → later obesity, mild–moderate intellectual disability.

Deletion on chromosome 18, short arm

Round face, large/low-set ears, mild–moderate intellectual disabilit

Deletion on chromosome 18, long arm

Distinctive mouth shape, small hands, small head, intellectual disability

Inversion

chromosome segment inverted 180 degrees

paracentric and pericentric

Pericentric Inversion

Chromosome inversion that includes the centromere in the inverted region

Paracentric Inversion

Inversions that do not include the centromere

Effect of Inversions (1)

Inversions in Meiosis

Individuals homozygous: no problems arise during meiosis

Heterozygous individuals

• Homologous sequences align only if the two
  chromosomes form an inversion loop

• Demonstrate reduced recombination in a paracentric
  Inversion, as gametes are formed results in nonviable offspring

• Have abnormal gametes formed in a pericentric inversion

Effect of Inversions (2)

In a heterozygous individual, a single crossover within a paracentric inversion leads to abnormal gametes.

Dicentric

Effect of Inversions (3)

In a heterozygous individual, a single crossover within a pericentric inversion leads to abnormal gametes

Translocations

Movement of a chromosome segment to a non-homologous chromosome or to another region of the same chromosome without reciprocal exchange

nonreciprocal, reciprocal, robertsonian,

Nonreciprocal Translocation

Movement of a chromosome segment to a nonhomologous chromosome or to another region of the same chromosome without reciprocal exchange

Reciprocal Translocation

Exchange between segments of a nonhomologous chromosome or to another region of the same chromosome

Robertsonian Translocation

The long arms of two acrocentric chromosomes become joined to a common centromere, generating a metacentric chromosome with two long arms and another chromosome with two very short arms

Effects of translocation

In an individual heterozygous for a reciprocal translocation, crosslike structures form in homologous pairing

Aneuploidy

change in number of individual chromosomes

caused by:

• deletion of centromere during mitosis and meiosis

• robertsonian translocation

• nondisjunction during meiosis

types: monosomy, trisomy, tetrasomy, nullisomy

Types of Aneuploidy

Nullisomy: loss of both members of a homologous pair (2n-2)

Monosomy: loss of a single chromosome (2n-1)
Trisomy: gain of a single chromosome (2n+1)

Tetrasomy: gain of two homologous chromosomes (2n+2)

Effects of Aneuploidy (1)

In plants: 

• Trisomics deviate from wild type

In humans: Sex-chromosome aneuploids:

• Turner Syndrome: XO

• Klinefelter Syndrome: XXY

Effects of Aneuploidy (2)

Trisomy 21: Down Syndrome

• Primary Down Syndrome: 75% random nondisjunction in egg formation

• Familial Down Syndrome: Robertsonian translocation between chromosomes 14 and 21

Effects of Aneuploidy (3)

Autosomal Aneuploids:

• Trisomy 18: Edward syndrome, 1/8000 live births

• Trisomy 13: Patau syndrome, 1/15,000 live births

• Trisomy 8: 1/25,000 ~ 1/50,000 live births

Why is there a drastic decrease in frequency of this
trisomic syndrome from chromosome 18 to
chromosome 8?

The larger the chromosome, the lower the frequency of live-born trisomic syndromes, because extra copies of many genes are usually lethal.

Effect of Aneuploidy (3)

Aneuploidy and Maternal Age

Nondisjunction happens more often as mothers get older, leading to a higher chance of giving birth to a child with down syndrome

Why sex-chromosome aneuploids are more common than autosomal aneuploids in humans and mammals?

Sex chromosomes tolerate dosage changes better, so their aneuploidies are more likely to survive to birth

Autopolyploidy

All chromosome sets are from a single species

Meiosis in Autopolyploid

In meiosis in an autotriploid, homologous chromosomes can pair, or fail to pair, in three ways. This example illustrates the pairing and segregation of a single homologous set of chromosomes.

Allopolyploidy

The chromosome sets are from two or more species

Species A has 2n=16 chromosomes and species B has 2n=14. How many chromosomes would be found in an allotriploid

16 + 7 = 23

14+ 8 = 22

22 or 23