Skip to main content
Sign In

Tamim H. Shaikh, PhD

Professor of Pediatrics

Director, Human Medical Genetics and Genomics Graduate Program​

   Phone: (303) 724-5399
   Fax:     (303) 724-3800

Genetics and Metabolism, Department of Pediatrics
Colorado Intellectual & Developmental Disabilities Research Center
Human Medical Genetics and Genomics Program​

  • Postdoctoral Fellow, Mentor - Dr. Beverly Emanuel,  Division of Human Genetics and Molecular Biology, The Children’s Hospital of Philadelphia (July 1995-June 1999)
  • Ph.D., Biochemistry & Molecular Biology, Advisor: Dr. Prescott Deininger, Louisiana State University Medical Center (1995)
  • B.Sc., Life Sciences & Biochemistry, St. Xavier's College, Bombay University, India (1988)

Copy Number Variation in Health and Disease: Copy number variations (CNVs) are a significant source of variation between individual genomes. CNV also play an important role in disease pathology, both Mendelian and common, complex disorders. We focus on genetic diseases that arise from genomic rearrangements, which can lead to CNV formation, including microdeletions, microduplications and unbalanced inversions or translocations. Diseases arising from such structural rearrangements have been designated “genomic disorders” which can manifest phenotypically as multiple congenital anomalies (MCA), including global developmental delay, intellectual disabilities and deficits, cardiac defects and cranio-facial differences.  We have assessed a large cohort of pediatric patients with MCA for copy number variations (CNVs) using high resolution microarrays and identified pathogenic CNVs that underlie the patients’ phenotype. We have also developed computational algorithms and databases for improved analysis of copy number data and assessment of the pathological significance of observed CNVs. The detection of increasingly smaller CNVs and determination of their role in disease continues to be a challenging problem. We continue to use increasingly higher resolution techniques, including next-generation optical mapping and long-read sequencing approaches for the detection of structural and copy number variations and study their association with Mendelian disorders as well as complex diseases and traits.

Genome Instability and Mechanisms of Rearrangement.: Another long-standing interest of my laboratory is understanding the mechanisms underlying the rearrangements that lead to genomic disorders. In several recurrent disorders, the rearrangements are often caused by aberrant recombination mediated by segmental duplications (SDs). SDs are a class of repetitive DNA elements in the human genome ranging in size from 1-500 kb and sharing >90% (typically 96-98%) sequence identity with each other. These regions of genomic instability make up ~5% of the human genome and play a major role in mediating structural and copy number variations in individuals with developmental disorders. Additionally, SDs have had a major impact on the evolution of the primate genome and continue to play a role in human disease and variation. Recent evidence from our work suggests that SD-containing regions are highly variable between individuals and populations. However, this type of variation has remained invisible due to limitations of past and most current sequencing technologies. We are now using next-generation optical mapping and long-read sequencing to map and characterize these regions more accurately. This will be an important first step towards elucidating the role of SDs in phenotypic variation and disease etiology.

Functional Analysis of Candidate Disease Genes.: In addition to CNV detection with SNP genotyping arrays and whole genome arrayCGH, we have also used whole exome/genome sequencing (WES/WGS) for genome-wide detection of pathogenic mutations in patient DNA. This work has led to the detection of numerous novel, pathogenic mutations including copy number variations (CNVs), single nucleotide variations (SNVs) and small insertion/deletions (indels) in a significant proportion of our patient cohort. As part of these studies, we have developed expertise in computational analysis of the CNV and high throughput sequence data. Functional analysis of the genes and mutations detected in our patients are followed up with other transcriptome analysis, using RNA-seq and ChIP-seq. We are also beginning to study the function of the candidate disease genes in both patient-derived cell lines as well as in model organisms including zebrafish and mouse. 

PubMed Bibliography​​

1: Demaerel W, Mostovoy Y, Yilmaz F, Vervoort L, Pastor S, Hestand MS, Swillen A,

Vergaelen E, Geiger EA, Coughlin CR, Chow SK, McDonald-McGinn D, Morrow B, Kwok

PY, Xiao M, Emanuel BS, Shaikh TH, Vermeesch JR. The 22q11 low copy repeats are

characterized by unprecedented size and structural variability. Genome Res. 2019 

Sep;29(9):1389-1401. doi: 10.1101/gr.248682.119. PubMed PMID: 31481461; PubMed

Central PMCID: PMC6724673.

2: Feliciano P, Zhou X, Astrovskaya I, Turner TN, Wang T, Brueggeman L, Barnard

R, Hsieh A, Snyder LG, Muzny DM, Sabo A; SPARK Consortium, Gibbs RA, Eichler EE, 

O'Roak BJ, Michaelson JJ, Volfovsky N, Shen Y, Chung WK. Exome sequencing of 457 

autism families recruited online provides evidence for autism risk genes. NPJ

Genom Med. 2019 Aug 23;4:19. doi: 10.1038/s41525-019-0093-8. eCollection 2019.

PubMed PMID: 31452935; PubMed Central PMCID: PMC6707204.

3: Hu T, Kruszka P, Martinez AF, Ming JE, Shabason EK, Raam MS, Shaikh TH,

Pineda-Alvarez DE, Muenke M. Cytogenetics and holoprosencephaly: A chromosomal

microarray study of 222 individuals with holoprosencephaly. Am J Med Genet C

Semin Med Genet. 2018 Jun;178(2):175-186. doi: 10.1002/ajmg.c.31622. PubMed PMID:

30182442; PubMed Central PMCID: PMC6127867.

4: Shaikh TH. Copy Number Variation Disorders. Curr Genet Med Rep. 2017

Dec;5(4):183-190. doi: 10.1007/s40142-017-0129-2. Epub 2017 Oct 14. PubMed PMID: 

29732242; PubMed Central PMCID: PMC5931734.

5: Quintana AM, Yu HC, Brebner A, Pupavac M, Geiger EA, Watson A, Castro VL,

Cheung W, Chen SH, Watkins D, Pastinen T, Skovby F, Appel B, Rosenblatt DS,

Shaikh TH. Mutations in THAP11 cause an inborn error of cobalamin metabolism and 

developmental abnormalities. Hum Mol Genet. 2017 Aug 1;26(15):2838-2849. doi:

10.1093/hmg/ddx157. PubMed PMID: 28449119; PubMed Central PMCID: PMC5886234.

6: Rachubinski AL, Hepburn S, Elias ER, Gardiner K, Shaikh TH. The co-occurrence 

of Down syndrome and autism spectrum disorder: is it because of additional

genetic variations? Prenat Diagn. 2017 Jan;37(1):31-36. doi: 10.1002/pd.4957.

Epub 2016 Nov 24. PubMed PMID: 27859447.

7: Van Laarhoven PM, Neitzel LR, Quintana AM, Geiger EA, Zackai EH, Clouthier DE,

Artinger KB, Ming JE, Shaikh TH. Kabuki syndrome genes KMT2D and KDM6A:

functional analyses demonstrate critical roles in craniofacial, heart and brain

development. Hum Mol Genet. 2015 Aug 1;24(15):4443-53. doi: 10.1093/hmg/ddv180.

Epub 2015 May 13. PubMed PMID: 25972376; PubMed Central PMCID: PMC4492403.

8: Mlynarski EE, Sheridan MB, Xie M, Guo T, Racedo SE, McDonald-McGinn DM, Gai X,

Chow EW, Vorstman J, Swillen A, Devriendt K, Breckpot J, Digilio MC, Marino B,

Dallapiccola B, Philip N, Simon TJ, Roberts AE, Piotrowicz M, Bearden CE, Eliez

S, Gothelf D, Coleman K, Kates WR, Devoto M, Zackai E, Heine-Suñer D, Shaikh TH, 

Bassett AS, Goldmuntz E, Morrow BE, Emanuel BS; International Chromosome 22q11.2 

Consortium. Copy-Number Variation of the Glucose Transporter Gene SLC2A3 and

Congenital Heart Defects in the 22q11.2 Deletion Syndrome. Am J Hum Genet. 2015

May 7;96(5):753-64. doi: 10.1016/j.ajhg.2015.03.007. Epub 2015 Apr 16. PubMed

PMID: 25892112; PubMed Central PMCID: PMC4570279.

9: Coughlin CR 2nd, Scharer GH, Friederich MW, Yu HC, Geiger EA, Creadon-Swindell

G, Collins AE, Vanlander AV, Coster RV, Powell CA, Swanson MA, Minczuk M, Van

Hove JL, Shaikh TH. Mutations in the mitochondrial cysteinyl-tRNA synthase gene, 

CARS2, lead to a severe epileptic encephalopathy and complex movement disorder. J

Med Genet. 2015 Aug;52(8):532-40. doi: 10.1136/jmedgenet-2015-103049. Epub 2015

Mar 18. PubMed PMID: 25787132.

10: Yu HC, Sloan JL, Scharer G, Brebner A, Quintana AM, Achilly NP, Manoli I,

Coughlin CR 2nd, Geiger EA, Schneck U, Watkins D, Suormala T, Van Hove JL, Fowler

B, Baumgartner MR, Rosenblatt DS, Venditti CP, Shaikh TH. An X-linked cobalamin

disorder caused by mutations in transcriptional coregulator HCFC1. Am J Hum

Genet. 2013 Sep 5;93(3):506-14. doi: 10.1016/j.ajhg.2013.07.022. PubMed PMID:

24011988; PubMed Central PMCID: PMC3769968.