Molecular Development - Genetics

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Contents

Introduction

Human idiogram

Genetics (Greek, genetikos = “origin”) and embryology have merged to such an extent that the two cannot now be separated from each other. The strong evolutionary conservation of developmental mechanisms has been astounding. Currently, much of modern medicine is a search for a disease gene and having found it, embryology is usually employed in understanding its mechanism. Embryological development begins with meiosis and is after all the opportunity for a specific genome to be expressed, regulated and utilized as it will never be again in the adult animal.

In combination with our statistical understanding of congenital abnormalities there now exist a large number of clinical tests for inherited abnormalities. This particular section of the notes is a link to bind our understanding of genetics with its relevance to development. There are several pages on DNA and links from the computer activities below to relevant sections. You can jump right in and look through the DNA database for a gene of interest using a keyword, or browse through the human genome by chromosome or by genetic diseases that have been identified. Or you can work through an exercise in using genetic databases for diseases.

See also the list of mouse gene knockouts which has made the geneticists not only use embryological tools, but also go back and learn some embryology. Recent research has also focussed on the new science of Epigenetics, the inheritance mechanisms that lie outside the actual DNA sequence of our genes.


Molecular Links: Introduction | Genetics | Epigenetics | Mitosis | Meiosis | X Inactivation | Signaling | Factors | Mouse Knockout | microRNA | Mechanisms | Developmental Enhancers | Protein | Genetic Abnormal | Category:Molecular


Genetic Links: Introduction | Genetic risk maternal age | Trisomy 21 | Trisomy 18 | Trisomy X | Fragile X | Williams | Philadelphia chromosome | Prenatal Diagnosis | Neonatal Diagnosis | International Classification of Diseases | Molecular Development - Genetics

Some Recent Findings


Chromatin Structure

Chromosome structure
Chromatin Structure.png
The folding of DNA and associated protein to form a chromosome.

Chromosome Banding

Trisomy 21 Female Karyotype G-banding stain.

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.

Depending on the type of stain used a number of different banding patterns can be seen:

  • G-banding - banding pattern seen by treating with trypsin and then staining with the dye giemsa.
  • R-banding - banding pattern seen as a of reverse giemsa chromosome banding, producing bands complementary to G-bands often used to determine whether there are deletions. Can be fluorescent using the dye acridine orange.
  • Q-banding - banding pattern seen by treating with a fluorochrome or the fluorescent dye quinacrin.
  • C-banding - banding pattern seen for centromeric or constitutive heterochromatin, the centromere appears as a stained band compared to other regions.


Metaphase is a cell division term referring to the third mitotic stage, mitotic spindle kinetochore microtubules align chromosomes in one midpoint plane. Metaphase ends when sister kinetochores separate. Originally based on light microscopy of living cells and electron microscopy of fixed and stained cells. A light microscope analysis called a "metaphase spread" was originally used to detect chromosomal abnormalities in cells.


Links: Histology Stains

Human Genome

Human Genome Length 3,101,788,170 bp. Mitochondrial Genome 16,568 bp.


Links: Human Genome Project (HGP) | NCBI Human Genome Resources | History of the Human Genome Project | Project Timeline


Nuclear Genome

Human idiogram

Mitochondrial Genome

Eukaryotic mitochondrial genomes
  • In humans this genome is maternally inherited.
  • Exists as multiple copies within the matrix of each mitochondrion within the cytoplasm of cells.
  • In 1981 the human mitochondrial genome was sequenced.
  • The genome is a small circular DNA molecule 16,568 bp in length containing 37 genes.
    • 24 genes specify RNA molecules involved in protein synthesis (22 transfer RNAs (tRNA) and 2 ribosomal RNAs (rRNA))
    • 13 genes encode proteins required for the biochemical reactions that make up respiration.

Swapping mitochondrial DNA mammalian oocytes.jpg

Swapping mitochondrial DNA mammalian oocytes[2] Assisted Reproductive Technology


Links: Mitochondria | 16569 bp Homo sapiens mitochondrion | Mitochondrial DNA Deletion Syndromes

Chromosome Regions

Chromosome Abnormalities

Ploidy refers to the chromosomal genetic content of cells. Euploidy (euploid) is the genetic term used to describe the normal cell genome chromosomal set (n, 2n, 3n) or complement for a species, in humans this is diploid (2n).

The terms used to describe the classes of numerical chromosomal abnormalities include:

  • Aneuploidy are chromosome mutations in which chromosome number is abnormal (increased or reduced), nondisjunction in meiosis or mitosis (anaphase of meiosis I, sister chromatids fail to disjoin at either meiosis II or at mitosis) is the cause of most aneuploids.
  • Polyploidy includes triploidy, usually due to two sperm fertilizing a single egg.
  • Mixoploidy includes mosaicism, where there are two or more genetically different cell lines in an individual.


Links: Abnormal Development - Genetic | Trisomy 21 | Trisomy 18 | Trisomy 13)

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

Inheritance Genetics

Pedigree chart


Inheritance Pattern images: Autosomal dominant inheritance | Autosomal recessive inheritance | X-Linked dominant (affected father) | X-Linked dominant (affected mother) | X-Linked recessive (affected father) | X-Linked recessive (carrier mother) | Mitochondrial genome inheritance | Codominant inheritance | Genogram symbols | Genetics

Genogram

A clinical diagram constructed to show an individual's family relationships and medical history, more detailed than a pedigree chart including non-genetic factors such as family emotional and social relationships. Additional colour coded symbols and connectors are used to show these relationships and interactions.


Genogram symbols.jpg

DNA Sequencing

Changes in genes can occur by a number of different methods including mutations, deletions and epigenetic modifications. Specific changes in DNA sequences can also be detected by a range of techniques, including direct sequencing of the DNA.

Recent technological developments have improved how DNA sequencing occurs and we are said to now be up to the "third generation" of sequencing techniques.[3]

DNA sequencing methods.jpg DNA sequencing methods third-generation.jpg
First and second generation sequencing[3] Third generation sequencing[3]

Using Genetic Databases

This exercise is an exploration of the available WWW and other database resources that relate to Human genetic diseases. The exercise is to explore the Human genome and its relationship to examples of know human genetic diseases that affect development and impact on health.

To start with, think of a specific Human disease and see what you can find out about:

  • Known gene?
  • What are the major effects of the disorder?
  • Does it have an effect/role in development?
  • Known mutations?
  • Likely hood of mortality?
  • History of the disease?
  • Who discovered the cause of the disease?
  • Most recent published data relationg to the disease?
  • What therapies are being explored?
  • Where to next?

References

  1. Eric A Shoubridge Developmental biology: Asexual healing. Nature: 2009, 461(7262);354-5 PMID:19759608
  2. 3.0 3.1 3.2 Eric E Schadt, Steve Turner, Andrew Kasarskis A window into third-generation sequencing. Hum. Mol. Genet.: 2010, 19(R2);R227-40 PMID:20858600 | Hum Mol Genet.

Online Textbooks

  • Genomes (2nd edition) Brown, T.A. New York and London: Garland Science ; c2002 PMID20821850
  • Introduction to Genetic Analysis Griffiths, Anthony J.F.; Miller, Jeffrey H.; Suzuki, David T.; Lewontin, Richard C.; Gelbart, William M. New York: W. H. Freeman & Co.; c1999
  • Modern Genetic Analysis Griffiths, Anthony J.F.; Gelbart, William M.; Miller, Jeffrey H.; Lewontin, Richard C. New York: W. H. Freeman & Co.; c1999
  • Human Molecular Genetics 2 Strachan, Tom and Read, Andrew P. New York and London: Garland Science; c1999
  • Genetics for Surgeons Morrison, Patrick J.; Spence, Roy A.J., authors Hatchwell, Eli, series editor London: Remedica; c2000
  • Sequence - Evolution - Function: Computational Approaches in Comparative Genomics Koonin, Eugene V; Galperin, Michael Y. Norwell (MA): Kluwer Academic Publishers ; c2003
  • The Genetic Landscape of Diabetes [Internet] Dean, Laura; McEntyre, J.R. Bethesda (MD): National Library of Medicine (US), NCBI; 2004 Jun
  • Madame Curie Bioscience Database Chapters taken from the Madame Curie Bioscience Database (formerly, Eurekah Bioscience Database) Eurekah.com and Landes Bioscience and Springer Science+Business Media; c2009

Reviews

Magdalena Götz, Wieland B Huttner The cell biology of neurogenesis. Nat. Rev. Mol. Cell Biol.: 2005, 6(10);777-88 PMID:16314867


Articles

Search PubMed

Not easy to generate a good search term for this topic.

Search "Genetic Development" All (151839) Review (31389) Free Full Text (54818)


Search Pubmed: Genetic Development | Genome

Genetic Terms

  • antisense - a sequence of DNA that is complementary usually to coding sequence of DNA or mRNA. Has been used experimentally to perturb or block gene expression. Also a mechanism that has been found to occur naturally as a regulatory mechanism.
  • autosomal inheritance - some hereditary diseases are described as autosomal which means that the disease is due to a DNA error in one of the 22 pairs that are not sex chromosomes. Both boys and girls can then inherit this error. If the error is in a sex chromosome, the inheritance is said to be sex-linked.
  • base - another term for nucleotide (usually a t c g).
  • base pair - Double stranded DNA has nucleotides A-T, C-G, paired by hydrogen bonds (2 for AT, 3 for GC). Note this means that GC is harder to separate that AT.
  • DNA - DeoxyriboNucleic Acid. The genetic material found in mammalian chromosomes and mitochondria. Consisting of 4 nucleic acids (ATCG) that combine in a triptych (3 nucleotide) code for protein amino acids (3nt=1aa).
  • DNA duplex - double stranded base-paired DNA forming a helix.
  • dominant inheritance - With autosomal dominant inheritance, there is an error in one of the 22 chromosome pairs. But the damaged gene dominates over the normal gene received from the other parent. If one of the parents has a disease caused by an autosomal dominant gene, all the children will have a 50 per cent risk of inheriting the dominant gene and a 50 per cent chance of not inheriting it. The children who do not inherit the damaged dominant gene will not themselves suffer from the disease, nor will they be able to pass the gene on to future children. This type of inheritance is present for example in Huntington's disease.
  • exon - a block of protein encoding sequence of DNA in a gene. Many proteins are made of several exons "stitched" or spliced together by editing out non-coding (intron) sequences.
  • fasta - a format for listing DNA sequence, where the first line has descritive information followed on the next line by the sequence without numbering.
  • GC repeat - a string of GC sequence repeated several times. Also associated with GC expansion, a mutational process that may lead eventually to serious gene expression effects.
  • gene - a sequence of DNA that encodes an individual protein.
  • genetic code - the 3 nucleotide sequence that forms a codon for a single amino acid or stop. See the gene code.
  • genome - the complete genetic information in the form of DNA available to a specific species.
  • hairpin loop - a folding of RNA generated by base pairing making a "===()" structure, the end loop and or stem of this structure can then interact with proteins or other RNA.
  • intron - a block of DNA within a gene not encoding a protein. Edited, spliced, out during transcription into mRNA. Originally thought not to contain any information, but more and more this appears not to be the case. Some intron sequences have been shown to regulate gene expression during development (eg c elegans, Lin 14)
  • karyotype - [Greek, karyon = kernel or nucleus + typos= stamp] The chromosomal makeup of a cell.
  • mRNA - messenger, transcribed from DNA in the nucleus and in mitochondria. Is translated by the ribosome in the cytoplasm (or mitochondrial matrix). Intermediate step in gene expression. (DNA-> mRNA-> protein).
  • mutation - any process which results in the alteration of the DNA sequence. Some conservative mutations may have no effect on the final amino acid encoded.
  • ploidy - refers to the chromosomal genetic content of cells.
  • point mutation - a change in a single nucleotide.
  • recessive inheritance - With autosomal recessive inheritance, the diseased individual has inherited the same gene damage from both father and mother. The damage is found on both chromosomes in the pair. But as this is not ´dominant gene damageª, neither father nor mother show any sign of disease, they are healthy carriers of the gene. We are all carriers of about five recessive genes of this type, but as spouses are seldom carriers of exactly the same damaged gene(s), all will probably go well in the next generation.
  • ribosome - complex of rRNA and ribosomal proteins, bind mRNA and translate it into protein.
  • RNA - RiboNucleic Acid. The intermediate nucleic acid involved in gene expression. It comes in 3 forms: tRNA, mRNA, rRNA.
  • rRNA - ribosomal, translates mRNA into protein. rRNA provides the "scaffolding" on which many ribosomal proteins are assembled as 2 subunits that themselves assemble to form a ribosome. rRNA genes are localized to the nucleolus in the nucleus, a sometimes visible region of DNA usually constantly being transcribed.
  • telomere - regions at the end of chromosomes. Shortening of the telomeres is thought to be associated with cellular aging. The enzyme that maintains the telomere is called telomerase. Introducing this gene into a cell can extend the cells lifespan.
  • transcription factor - a protein which binds to DNA activating (usually) gene expression. There are many different ways and forms that this activation can take place, but most transcription factors fall into specific classes (eg zinc fingers, helix loop helix).
  • tRNA - transfer, binds single amino acids acts as a "donor' for protein synthesis.

External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name.

https://main.g2.bx.psu.edu

Glossary Links

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


Cite this page: Hill, M.A. (2014) Embryology Molecular Development - Genetics. Retrieved April 23, 2014, from http://embryology.med.unsw.edu.au/embryology/index.php?title=Molecular_Development_-_Genetics

What Links Here?
Dr Mark Hill 2014, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G
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