This web page was produced as an assignment for Genetics 564, an undergraduate course at UW-Madison.
The NDN Gene
NDN is found on chromosome 15 of humans in the Prader-Willi syndrome deletion region between 15q11-q13. It is an intronless gene which means that all of the gene is coded into a protein without uncoded regions in between. In this situation, the gene is then the same length as the mRNA coded from it. NDN is imprinted on the maternal allele in this region, and is thus not expressed from the maternal allele, but only from the paternal allele (6). The main roles of NDN are in neural differentiation and as a growth suppressor facilitating the entry of the cell into cell cycle arrest (7).
Homology
What is Homology?
Homology is a similarity between different species across many different features such as structure or physiology (1). Characteristics or structures are considered to be homologous if they have evolved from the same characteristic or structure in their common ancestor (2). In order to conduct research using model organisms to find information about the human condition, it is important to understand how similar the structures, physiology, and genetics are between organisms (2). Indeed, the foundation of genetic homology is especially important when using model organisms to study human conditions as small changes to the nucleotide sequence could bring about big changes in the expression of the gene, leading to gaps between the model and human.
Homology of NDN
Homology is a similarity between different species across many different features such as structure or physiology (1). Characteristics or structures are considered to be homologous if they have evolved from the same characteristic or structure in their common ancestor (2). In order to conduct research using model organisms to find information about the human condition, it is important to understand how similar the structures, physiology, and genetics are between organisms (2). Indeed, the foundation of genetic homology is especially important when using model organisms to study human conditions as small changes to the nucleotide sequence could bring about big changes in the expression of the gene, leading to gaps between the model and human.
Homology of NDN
BLAST Results:
Using the Homo sapiens accession number found through Entrez, I was able to run a BLAST report finding the organisms with comparable NDN sequences to Homo sapiens. Using these homologs, I was able to conduct a Reciprocal BLAST so as to confirm my results. To the right is a table showcasing my BLAST results. The Max Score and Total Score comment on the quality of the sequence comparison, with higher being better (3). The Query Coverage allows us to know how much of the given sequence lines up with the Homo sapiens sequence it was compared to. The E Value shows statistical significance, with zero being the best option (3). Finally the Maximum Identity shows the percent identity between Homo sapiens and the given sequence based on nucleotide-to-nucleotide alignment (3).
Using the Homo sapiens accession number found through Entrez, I was able to run a BLAST report finding the organisms with comparable NDN sequences to Homo sapiens. Using these homologs, I was able to conduct a Reciprocal BLAST so as to confirm my results. To the right is a table showcasing my BLAST results. The Max Score and Total Score comment on the quality of the sequence comparison, with higher being better (3). The Query Coverage allows us to know how much of the given sequence lines up with the Homo sapiens sequence it was compared to. The E Value shows statistical significance, with zero being the best option (3). Finally the Maximum Identity shows the percent identity between Homo sapiens and the given sequence based on nucleotide-to-nucleotide alignment (3).
Pan troglodytes (Common Chimpanzee)
Necdin (NDN) Accession: XM_510257 Length: 1679 bp Odobenus rosmarus divergens (Walrus) Necdin (NDN) Accession: XM_004405483 Length: 1878 bp Canis Lupus (Gray Wolf) Necdin (NDN) Accession: XM_005618240 Length: 1695 bp Bos taurus (Domestic Cow) Necdin (NDN) Accession: BT029863 Length: 1630 bp |
Macaca mulatta (Rhesus Macaque)
Necdin (NDN) Accession: NM_001172102 Length: 1921 bp Spermophilus tridecemlineatus (Ground Squirrel) Necdin-like (NDN) Accession: XM_005340564 Length: 1652 bp Felis catus (Cat) Necind (NDN) Accession: XM_011282821 Length: 1664 bp Mus muscularis (House Mouse) Necdin (NDN) Accession: MUSNCP Length: 3899 bp |
Discussion of NDN Homology
NDN is pretty well conserved which makes sense as it is a gene found only in mammals, and mammals have had a relatively recent common ancestor. Base pair length varies among each organism, leading to a difference in query cover. This could be due to the human necdin sequence used being the DNA sequence including all of the extra transcription sequences whereas many of the model organisms had the mRNA sequence. This should not present much of a difference, functionally, as NDN is an intronless gene, so the DNA and mRNA sequences should line up well. Something interesting of note is the fact that Mus musculus has been the only model organism used in studying NDN function in relation to Prader-Willi Syndrome, and it has the least percent identity of the organisms listed.
NDN is pretty well conserved which makes sense as it is a gene found only in mammals, and mammals have had a relatively recent common ancestor. Base pair length varies among each organism, leading to a difference in query cover. This could be due to the human necdin sequence used being the DNA sequence including all of the extra transcription sequences whereas many of the model organisms had the mRNA sequence. This should not present much of a difference, functionally, as NDN is an intronless gene, so the DNA and mRNA sequences should line up well. Something interesting of note is the fact that Mus musculus has been the only model organism used in studying NDN function in relation to Prader-Willi Syndrome, and it has the least percent identity of the organisms listed.
Gene Ontology
What is Gene Ontology?
The ontology of something describes its state of being or its specific conception. Gene Ontology, then, is the basic description and conceptualization of the gene in subject. It is split into three factions: Cellular Component, Biological Process, and Molecular Function. The Cellular Component provides information on where in or out of the cell that the gene products localize. The Biological Process tells how the gene products broadly function in or out of the cell. The Molecular Function looks at the molecular mechanisms that the gene products take to proceed with its functioning.
The ontology of something describes its state of being or its specific conception. Gene Ontology, then, is the basic description and conceptualization of the gene in subject. It is split into three factions: Cellular Component, Biological Process, and Molecular Function. The Cellular Component provides information on where in or out of the cell that the gene products localize. The Biological Process tells how the gene products broadly function in or out of the cell. The Molecular Function looks at the molecular mechanisms that the gene products take to proceed with its functioning.
Discussion of NDN Ontology
Necdin localizes to many places within the cell leading to it having many different biological processes. The biological process that necdin is most known for is its regulation of growth, but it has many other processes as well. Notice that many of the processes have a role in neural development, implying that the deletion of this gene, as occurs in PWS, will lead to defects in neural development. It is also quite interesting that the only molecular function of this gene is DNA binding. This could be why necdin has a role in so many functions, as it must act as an activator or repressor of other gene products leading to these activities through binding to the DNA.
Necdin localizes to many places within the cell leading to it having many different biological processes. The biological process that necdin is most known for is its regulation of growth, but it has many other processes as well. Notice that many of the processes have a role in neural development, implying that the deletion of this gene, as occurs in PWS, will lead to defects in neural development. It is also quite interesting that the only molecular function of this gene is DNA binding. This could be why necdin has a role in so many functions, as it must act as an activator or repressor of other gene products leading to these activities through binding to the DNA.
References:
1. http://www.britannica.com/EBchecked/topic/270557/homology
2. Wagner, 2007 http://www.nature.com.ezproxy.library.wisc.edu/nrg/journal/v8/n6/full/nrg2099.html
3. http://www.garlandscience.com/res/pdf/practicalbioinformatics_ch3.pdf
1. http://www.britannica.com/EBchecked/topic/270557/homology
2. Wagner, 2007 http://www.nature.com.ezproxy.library.wisc.edu/nrg/journal/v8/n6/full/nrg2099.html
3. http://www.garlandscience.com/res/pdf/practicalbioinformatics_ch3.pdf