Popular TAM cultivars with excellent tolerance to drought, diseases, and insects were planted multiple million acres in the U.S. hard red winter wheat regions. The effects of the 1AL.1RS translocation, pest resistances from Aegilops tauschii, and other beneficial traits on yield, yield components, and end-use quality were analyzed using linkage and association mapping analyses. The allele effects from adapted cultivars and primary synthetics were estimated. Kompetitive allele specific PCR (KASP) markers were developed and validated for major genes, Wsm2 for wheat streak mosaic virus resistance, Gb3 and Gb7 for greenbug resistance, H32 for Hessian fly resistance, Cmc4 for wheat curl mite resistance, YrTAM111 for stripe rust resistance, and 2BS QTL for grain weight. The marker-assisted selection for major genes and genomic predictions/selections on minor genes will increase selection efficiencies during the germplasm and cultivar development.