ANAT2341 Lab 3 2013

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Human genetic diseases

This practical contains the first of a series of tutorials designed to support the group projects. We will discuss various techniques used to diagnose and identify the genetic abnormalities found in many human congential illnesses.

Objectives of this laboratory

  1. second short answer/ multiple choice test of last week's lecture material (Week 3 of human development)
  2. Tutorial on human genetic disorders, diagnosis, mapping and modern techniques such as genome sequencing.
  3. Provide time for groupwork and allow groups to ask questions of lecturing staff.

Human developmental diseases

There are many common and rare human genetic diseases. Some are due to mutations of a single gene - monogenic disorders e.g. Cystic Fibrosis, Duchenne Muscular Dystrophy Some are due to chromosomal abnormalities - polygenic disorders e.g. Williams-Beuren syndrome, Downs Syndrome

  1. (Some common genetic diseases) examples of specific genetic disorders NHGRI
  2. (Comprehensive database of human genetic disorders and associated genes) Online Mendelian Inheritance in Man OMIM

Diagnosis of human genetic diseases

  1. Clinical examination and assessment
  2. Personal history
  3. Family history
  4. Genetic tests

Genetic tests may include clinical cytogenetics which involves an examination of the chromosomes to look for evidence of aneuploidy, which means a loss or gain of the usual amount of genetic material, such as Trisomy 21 - Downs Syndrome. This will lead to changes in the number of copies of genes in the genome - a copy number variation or CNV.

This method will also pick up chromosomal rearrangements such as inversions or translocations. The breakpoints of these chromosomal rearrangements can lead to abnormal expression or complete loss of gene function as well as in some cases, creation of an abnormal chimeric fusion gene such as the Philadelphia Chromosome which causes a fusion of the genes BCR and ABL. The resulting protein leads to the development of chronic myelogenous leukaemia.

Standard methods can only identify large scale changes and rearrangements. However, since the development of Fluoresecence In-Situ Hybridisation (FISH) it is now possible to identify small scale changes such as microdeletions (e.g. Williams-Beuren Syndrome).


Human Chromosomes

Human idiogram
Human Chromosomes: 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | 21 | 22 | X | Y  
Idiogram Chromosome Banding - The term refers to the light and dark pattern, seen after staining with a dye, of individual chromosomes identified in metaphase. It is only in meiosis and mitosis during metaphase that chromosomes can be easily identified, during the normal cell life (interphase) the chromosomes are unravelled and distributed within the nucleus in chromosome territories. A band is that part of a chromosome which is clearly distinguishable from nearby regions by appearing darker or brighter with one or more banding techniques.
Human Idiogram: 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | 21 | 22 | X | Y
Genetic abnormality locations: 1-4 | 5-8 | 9-12 | 13-16 | 17-20 | 21-XY | sSMC
Inheritance Pattern images: Genetic Abnormalities | autosomal dominant | autosomal recessive | X-linked dominant (affected father) | X-Linked dominant (affected mother) | X-Linked recessive (affected father) | X-Linked recessive (carrier mother) | mitochondrial inheritance | Codominant inheritance | Genogram symbols | Genetics
Links: Genetics | Abnormal Development - Genetic

Cite this page: Hill, M.A. (2019, November 22) Embryology ANAT2341 Lab 3 2013. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/ANAT2341_Lab_3_2013

What Links Here?
© Dr Mark Hill 2019, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G


Some Human Disease Gene Locations

Human genetics chromosomes 1-4.jpg

Human genetics chromosomes 5-8.jpg

Human genetics chromosomes 9-12.jpg

Human genetics chromosomes 17-20.jpg

Human genetics chromosomes 21-XY.jpg

Genetic Inheritance

The figures below show the pattern of inheritance of a range of genetic disorders. In addition to these patterns are the known effects of increased maternal age and the effects of genetic mutations in the embryo and newborn.

Inheritance Pattern images: Genetic Abnormalities | autosomal dominant | autosomal recessive | X-linked dominant (affected father) | X-Linked dominant (affected mother) | X-Linked recessive (affected father) | X-Linked recessive (carrier mother) | mitochondrial inheritance | Codominant inheritance | Genogram symbols | Genetics

An example of autosomal recessive traits are the majority of 50 or so lysosomal diseases, with two X-linked exceptions, that of Fabry disease and Mucopolysaccharidosis II.[1]

Trisomy

In humans, the most common trisomy is trisomy 21 or Down syndrome.

The term trisomy refers to the abnormal copy number of a specific chromosome, that is 3 copies instead of 2. The abnormality is identified by the chromosome that is present as 3 copies within the cell.

Linkage analysis

Identification of genetic mutations causing a disease are sometimes unknown and a common strategy to map the location of the mutation is to use linkage analysis. This strategy relies on establishing a family group with some affected by the disease and other that are unaffected. The larger the family, or the greater the number of different families with the same disease, the greater the power of the mapping approach. This technique relies on the knowledge that chromosomes recombine during meiosis. Small regions of chromosomes will generally be inherited as a series of single intact pieces. However, the larger the region, the greater the likelihood that it will be divided by meiotic recombination. By looking for correlation between segregation of the disease and co-segregation of genetic markers distributed all over the human genome, it is possible to identify chromosomal sites where specific markers are always (or nearly always) inherited when the disease is present. Once the specific chromosomal region has been mapped, genes in the vicinity must be identified and candidate genes that look likely to be causative can be sequenced to look for specific changes that might explain the defect.

Genetic mapping of Mendelian characters

Modern methods in human genetics

Genome-wide association study (GWAS)

The National Human Genome Research Institute (USA) lists publications as part of the genome-wide association study (GWAS) in an attempt to assay at least 100,000 single nucleotide polymorphisms (SNPs) in the initial stage.

Links: Genome-wide association study | National Human Genome Research Institute

GWAS is mostly used in large sample groups of the human population to look for genes that predispose individuals towards specific common diseases such as coronary artery disease or type I diabetes. The first successful GWAS study was published in 2005 on age-related macular degeneration. Complement factor H polymorphism in age-related macular degeneration


Glossary Links

Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link

Cite this page: Hill, M.A. (2019, November 22) Embryology ANAT2341 Lab 3 2013. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/ANAT2341_Lab_3_2013

What Links Here?
© Dr Mark Hill 2019, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G
  1. <pubmed>2050994</pubmed>| Orphanet J Rare Dis.