Final answer:
In sexual reproduction, meiosis is responsible for gene reshuffling that leads to genetic variation in offspring, through processes such as crossover, random assortment, and fertilization.
Step-by-step explanation:
The process responsible for gene reshuffling and the generation of new genetic combinations during sexual reproduction is meiosis. During meiosis, several mechanisms contribute to genetic variation: crossover (where chromosomes exchange genetic material), random assortment of homologous chromosomes (where chromosomes are distributed into gametes randomly), and subsequently, fertilization, which is the fusion of two haploid gametes from different parents. These processes collectively ensure that offspring have a unique genetic makeup different from both parents.