Additional file 1: Figure S1A. of A patient with van Maldergem syndrome with endocrine abnormalities, hypogonadotropic hypogonadism, and breast aplasia/hypoplasia

Pathways of estrogen activation of gene transcription (Classic): E2 = Estradiol, ER = Estrogen Receptor, ERE = Estrogen Receptor Elements. Estrogen (estradiol, E2) is the major factor in promoting breast development by activating the estrogen receptor Îą (ESR1) but there are different pathways; the classic genomic pathway and alternatives. In the classic pathway (Figure S1, A), the activated ESR1 dimerizes, binds with high affinity and specificity to DNA sequences called estrogen response elements (EREs) to regulate transcription rates of target genes. Activated ESR1 then recruits-interacts with steroid receptor co-regulators (SRCS) and chromatin remodelers that facilitate access to chromatin and coordinate transcription of the transcriptional modulators. Transcription is facilitated or impeded in part by modifications of histones, the more abundant proteins in the nucleus which package the DNA. Modification of histones by acetylation via histone acetyl transferases or deacetylation via histone deacetylases affects transcription of genes [22]. Figure S1B. There are alternative mechanisms of action when the estrogen receptor can sometimes regulate expression of genes that lack EREs resulting in activation of reporter genes containing activator protein 1 (Ap-1) elements (Figure S1, B). Through protein-protein interaction, estrogen receptors can modulate the transcriptional activity of heterodimers of the transcription factors fos and jun (Ap-1 responsive elements), leading to activation of reporter genes containing Ap-1 elements. This non-classical genomic pathway is also functional in vivo. Ap-1 is a transcription factor complex containing the proto-oncogenes jun/fos and other family members. This complex interacts with Ap-1 sites in gene promoters to activate a large number of genes involved in cellular differentiation and development [16]. (DOCX 96 kb

Gene-resolution analysis of DNA copy number variation using oligonucleotide expression microarrays-2

<p><b>Copyright information:</b></p><p>Taken from "Gene-resolution analysis of DNA copy number variation using oligonucleotide expression microarrays"</p><p>http://www.biomedcentral.com/1471-2164/8/111</p><p>BMC Genomics 2007;8():111-111.</p><p>Published online 30 Apr 2007</p><p>PMCID:PMC1868757.</p><p></p>r differences at 140 to 228 Mb of chromosome 1, where SK-N-SH/L shows gain while SK-N-SH/G shows normal DNA content. Segmentation analysis of BAC aCGH (A) and graCNV (B) highlight the same region as amplified. log2 copy numbers inferred from CBS are shown as red (SK-N-SH/G) and blue (SK-N-SH/L) lines

Gene-resolution analysis of DNA copy number variation using oligonucleotide expression microarrays-0

<p><b>Copyright information:</b></p><p>Taken from "Gene-resolution analysis of DNA copy number variation using oligonucleotide expression microarrays"</p><p>http://www.biomedcentral.com/1471-2164/8/111</p><p>BMC Genomics 2007;8():111-111.</p><p>Published online 30 Apr 2007</p><p>PMCID:PMC1868757.</p><p></p> genomic DNAs (C2, C4, C5 and C6) and neuroblastoma cell lines (SK-N-SH/G, SK-N-SH/L, SK-N-AS and IMR-32). log2 copy number estimates calculated by WPP (left) and RMA (right) were analyzed for relative distance by PCA (top) and by hierarchical clustering (bottom). RMA separates two closely related cell lines (SK-N-SH/G and SK-N-SH/L) in PCA (Fig. 1B) and clustering (Fig. 1D), while WPP groups them together (Fig. 1A and C), clearly separated from normal genomic DNAs

Gene-resolution analysis of DNA copy number variation using oligonucleotide expression microarrays-3

<p><b>Copyright information:</b></p><p>Taken from "Gene-resolution analysis of DNA copy number variation using oligonucleotide expression microarrays"</p><p>http://www.biomedcentral.com/1471-2164/8/111</p><p>BMC Genomics 2007;8():111-111.</p><p>Published online 30 Apr 2007</p><p>PMCID:PMC1868757.</p><p></p>is from graCNV data (C), but only the amplicon at 67 Mb from BAC aCGH data (A). In SK-N-SH/G cells, a deletion on chromosome 8 at 39.5 Mb was inferred from graCNV data (D), but not from BAC aCGH data (B). Physical positions are shown at the x-axis in units of 1000

Gene-resolution analysis of DNA copy number variation using oligonucleotide expression microarrays-4

<p><b>Copyright information:</b></p><p>Taken from "Gene-resolution analysis of DNA copy number variation using oligonucleotide expression microarrays"</p><p>http://www.biomedcentral.com/1471-2164/8/111</p><p>BMC Genomics 2007;8():111-111.</p><p>Published online 30 Apr 2007</p><p>PMCID:PMC1868757.</p><p></p>re shown by asterisks; the bracket shows the region of variable copy numbers (A). Pulsed field electrophoresis analysis of the C4/CYP21A2 region of four individuals showing two copies (C2), four copies (C4), five copies (C5) and six copies (C6) of the region. The ruler to the left shows fragment size in kb; observed long and short alleles are indicated by L and S respectively (B). graCNV analysis of chromosome 6 at 32,045 kb to 32,194 kb; log2 copy number differences are shown relative to individual C2 (two copies) for individuals C4 (light gray, four copies), C5 (dark gray, five copies) C6 (black, 6 copies)

Gene-resolution analysis of DNA copy number variation using oligonucleotide expression microarrays-5

<p><b>Copyright information:</b></p><p>Taken from "Gene-resolution analysis of DNA copy number variation using oligonucleotide expression microarrays"</p><p>http://www.biomedcentral.com/1471-2164/8/111</p><p>BMC Genomics 2007;8():111-111.</p><p>Published online 30 Apr 2007</p><p>PMCID:PMC1868757.</p><p></p>ese genes in homozygous mutants of the megabladder mouse was observed by graCNV (A) and confirmed by quantitative PCR (B). Differential gene expression between homozygous mutants and wild type shows overexpression of four of the amplified genes in whole embryos (C) and overexpression of three genes in the target organ, the embryonic bladder (D). (E) Interphase FISH analysis of a homozygous megabladder mutant shows two copies of chromosome 11 (green) and four copies of the duplicated region of chromosome 16 at 27.0 Mb (red)

Gene-resolution analysis of DNA copy number variation using oligonucleotide expression microarrays-1

<p><b>Copyright information:</b></p><p>Taken from "Gene-resolution analysis of DNA copy number variation using oligonucleotide expression microarrays"</p><p>http://www.biomedcentral.com/1471-2164/8/111</p><p>BMC Genomics 2007;8():111-111.</p><p>Published online 30 Apr 2007</p><p>PMCID:PMC1868757.</p><p></p>ept for chromosome 2 (-2 to +8). log2 copy numbers inferred from CBS are shown as red lines for segments > 1 Mb. Measurements are plotted along the physical map of chromosomes