Human GeneticsHuman Genetics

The study of human genetics The study of human genetics requires alternative methods requires alternative methods

Studies of pedigrees are problematic Studies of pedigrees are problematic because human families are smallbecause human families are small

KaryotypKaryotypee

Karyotyping is the analysis of Karyotyping is the analysis of chromosomes chromosomes

Cytogenetics is the study of Cytogenetics is the study of chromosomes and inheritance chromosomes and inheritance

Cytogenetics is based on studies of Cytogenetics is based on studies of humans as well as humans as well as DrosophilaDrosophila and and other organismsother organisms

PPreparing a karyotypereparing a karyotype

1.1. HHarvested cells are first cltured arvested cells are first cltured 2.2. The cells are then treated with colchicine which The cells are then treated with colchicine which

arrests the cells in metaphase, and then treated arrests the cells in metaphase, and then treated and stained to observe the chromosomes and stained to observe the chromosomes

3.3. Chromosomes can be photographed or Chromosomes can be photographed or visualized using a computer, and then analyzed visualized using a computer, and then analyzed

4.4. Chromosomes are identified by size, position of Chromosomes are identified by size, position of the centromere, and banding and staining the centromere, and banding and staining regionsregions

Why Analyse Chromosomes and Genes?

Genetic errors arise from deletions or insertions of genetic material, abnormal numbers of whole chromosomes or genes, and even from misplacement of a single base in the DNA sequence.

Genetic abnormalities can range from relatively harmless to severe: from vitamin deficiencies and food allergies to cancer, birth defects and infant mortality.

Chromosomal Chromosomal abnormalitiesabnormalities

AAutosome utosome chromosomal chromosomal abnormalities abnormalities SexSex chromosomal chromosomal abnormalities abnormalities

Both could be affected in the structure Both could be affected in the structure or the number of the chromosomesor the number of the chromosomes

Abnormalities in chromosome Abnormalities in chromosome number cause certain human number cause certain human disordersdisorders

A.A. PolyploidyPolyploidy

B.B. AneuploidyAneuploidy

PolyploidyPolyploidy

A.A. Polyploidy is the presence of Polyploidy is the presence of additional sets of chromosomesadditional sets of chromosomes

1.1. Polyploidy is common in plants Polyploidy is common in plants

2.2. Polyploidy is typically lethal in animals Polyploidy is typically lethal in animals

3.3. Polyploidy is due to nondisjunction or Polyploidy is due to nondisjunction or multiple fertilizations of an eggmultiple fertilizations of an egg

AneuploidyAneuploidy

B. B. Aneuploidy is a condition of an extra Aneuploidy is a condition of an extra chromosome chromosome

1.1. ExtraExtra chromosome chromosome:: trisomic for a trisomic for a particular chromosome particular chromosome

2.2. OOr a missing chromosomer a missing chromosome: : haploid for haploid for that chromosome that chromosome

Aneuploidies result from nondisjunction Aneuploidies result from nondisjunction during meiosis or mitosisduring meiosis or mitosis

Down syndromeDown syndrome

Persons with Down syndrome are usually Persons with Down syndrome are usually trisomic for chromosome 21 trisomic for chromosome 21

1.1. Down syndrome is a relatively common Down syndrome is a relatively common chromosomal abnormality chromosomal abnormality

2.2. Morphological characteristics include Morphological characteristics include differences in the face, tongue, and hands, differences in the face, tongue, and hands, and individuals are mentally retarded and individuals are mentally retarded

3.3. Down syndrome is typically caused by a Down syndrome is typically caused by a trisomy of chromosome 21, usually caused trisomy of chromosome 21, usually caused by nondisjunction during oogenesis by nondisjunction during oogenesis

4. 4. Down syndrome is much more common in Down syndrome is much more common in babies with older mothers, perhaps babies with older mothers, perhaps because an older woman is less likely to because an older woman is less likely to spontaneously abort a Down fetusspontaneously abort a Down fetus

5. 5. Affected individuals may vary in the severity Affected individuals may vary in the severity of their symptomsof their symptoms

6. 6. Other trisomies are typically inviable, as are Other trisomies are typically inviable, as are monosomiesmonosomies

SSex chromosomex chromosomal abnormalties al abnormalties

Most sex chromosome aneuploidies Most sex chromosome aneuploidies are less severe than autosome are less severe than autosome abnormalities abnormalities

Klinefelter syndromeKlinefelter syndrome

1.1. Individuals with Klinefelter syndrome Individuals with Klinefelter syndrome have an XXY karyotype have an XXY karyotype

2.2. Klinefelter males have small testes Klinefelter males have small testes and are often sterileand are often sterile

3.3. Klinefelter males are often tall and Klinefelter males are often tall and have female-like breast development; have female-like breast development; about half are mentally impairedabout half are mentally impaired

Turner syndromeTurner syndrome

1.1. Persons with Turner syndrome have only Persons with Turner syndrome have only one X chromosome and no Y one X chromosome and no Y chromosomechromosome

2.2. Turner syndrome females are designated Turner syndrome females are designated as XO, and have undeveloped as XO, and have undeveloped reproductive structures and are sterilereproductive structures and are sterile

3.3. No Barr bodies are apparent in persons No Barr bodies are apparent in persons with Turner syndromewith Turner syndrome

XYYXYY Disorders Disorders

1.1. Some essentially normal males have Some essentially normal males have an XYY karyotype an XYY karyotype

a.a. Persons with an extra Y chromosome Persons with an extra Y chromosome are fertile, phenotypically male, and are fertile, phenotypically male, and often are very tall and have acneoften are very tall and have acne

Aneuploidies usually result in prenatalAneuploidies usually result in prenatal d deatheath

• Chromosome abnormalities are relatively Chromosome abnormalities are relatively common at conception but usually result in common at conception but usually result in a miscarriage a miscarriage

• Approximately 20% of all pregnancies may Approximately 20% of all pregnancies may be spontaneously aborted, often due to be spontaneously aborted, often due to major chromosomal abnormalitiesmajor chromosomal abnormalities

Abnormalities in chromosome Abnormalities in chromosome structure cause certain disordersstructure cause certain disorders

TranslocationTranslocation Translocation is attachment of part of Translocation is attachment of part of

a chromosome to a nonhomologous a chromosome to a nonhomologous chromosome chromosome

This is the cause of approximately This is the cause of approximately 4% of Down syndrome4% of Down syndrome

DDeletioneletion A deletion is loss of part of a A deletion is loss of part of a

chromosome chromosome Most large deletions are nonviable Most large deletions are nonviable An example of a deletion is the cri-An example of a deletion is the cri-

du-chat syndromedu-chat syndrome

Fragile sitesFragile sites Fragile sites are weak points at Fragile sites are weak points at

specific sites in chromatids specific sites in chromatids Fragile sites appear to be held Fragile sites appear to be held

together by thin strands of chromatin together by thin strands of chromatin Fragile X syndrome is a relatively Fragile X syndrome is a relatively

common cause of mental retardation, common cause of mental retardation, particularly in malesparticularly in males