Cytogenetics? 1870 the Study of Chromosomal Changes in Cells for Diagnosis Waleyer-Hartz Coins the Term Or Treatment

Evolution of cytogenetic techniques 20,000 genes 46 chromosomes 23 pairs Karyotyping FISH Microarrays NGS

Innovation and discovery

Nägeli identiﬁ es chromosomes for the ﬁ rst time. 1842

What is Flemming uses aniline dye to observe chromosomes. cytogenetics? 1870 The study of chromosomal changes in cells for diagnosis Waleyer-Hartz coins the term or treatment. 1888 “chromosomes.”

Tjio and Levan determine that humans have 46 chromosomes. Key contributors 1956

Lejeune discovers that people with Down syndrome (trisomy 21) have an extra chromosome. Karl Nägeli 1959 (1817–1891) Swiss Botanist The ﬁ rst International System for Chromosome Nomenclature (ISCN) conference is held. Published a paper on the 1960 development of pollen and the “transitory cytoblasts” that were later identiﬁ ed as chromosomes. Scientists develop G-banding, C-banding, and reverse banding. 1971

Bauman, Wiegant, Borst, and van Dujin use FISH (ﬂ uorescence Walther Flemming in situ hybridization). (1843–1905) 1980 German Anatomist Observed and described the behavior Pinkel and Gray add interphase and metaphase FISH for clinical diagnostics. of chromosomes during cell division. 1986-88

Southern ﬁ les a UK patent application for in situ synthesized, oligonucleotide microarrays. Joe Hin Tjio, PhD 1988 (1919–2001) American Geneticist Fodor and colleagues publish the photolithographic array fabrication method. Found that human cells contain 1991 46 chromosomes arranged as 23 pairs.

Schena publishes the fi rst use of microarrays 1995 for gene expression analysis. Joe W. Gray, PhD & Daniel Pinkel, PhD Schrock and Ried describe multicolor spectral karyotyping. Applied FISH in a clinical setting to 1996 visualize chromosomes. The American College of Medical Genetics (ACMG) recommends replacing karyotyping with chromosomal 2010 microarrays as a fi rst-line postnatal test. Edwin Southern, PhD Filed the fi rst patent application for in situ Microarray technology is synthesized, oligonucleotide microarrays applied to prenatal diagnostics. in the United Kingdom. 2012 ACMG recommends the use of prenatal chromosomal microarray analysis to monitor a fetus with one or more major structural abnormalities. 2013

Current and future applications Building on history and forging new paths

Technologies have been applied and advanced for more than a century, helping scientists understand chromosome defects and rearrangements. Their ability to examine genetic material at the nucleotide level has opened a world of exciting possibilities.

Genetic diseases Common genetic Chromosome Birth defects disorders research Fetal loss Down syndrome White blood cells Developmental delays Turner syndrome Bone marrow cells Cystic ﬁ brosis Fetal cells Genetic diseases = mutation in chromosomal structure Huntington’s disease Chromosomes are often extracted from live cells.

Early visualization: FISH Comparative genomic karyotyping First described in the late hybridization Aniline dyes were used 1960s and later achieved Has better resolution than to witness chromosome widespread use G-banding or FISH behavior during mitosis Helps detect single genes, Used to detect Techniques like specifi c regions, and chromosomal copy number G-banding, C-banding, whole chromosomes variations (CNVs) and Q-banding were Off ers speed, sensitivity, Can help fi nd abnormalities established stability, and convenience in prenatal and neonatal Spectral karyotyping and Does not allow for effi cient genomes multicolor FISH (mFISH) break point mapping for Cannot be used to identify revolutionized the fi eld in chromosome structural chromosome the 1970s and 80s translocations aberrations Limitations: Karyotyping cannot detect small SNV abnormalities and it requires cell culture

Microarrays Next-generation Medical genetics sequencing researchers identiﬁ ed Short- and long-read single nucleotide sequencing continue to polymorphisms drive variant discovery in (SNPs) cytogenetic research Combined CGH with Custom testing options microarrays to catalog and like focused exome and assess variations in human whole exome sequencing genetics High levels of data Modern CNV and SNP complexity probe arrays oﬀ er greater insight across the whole genome