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The Y chromosome unveiled

Completing the human genome puzzle with the missing piece

A brief history of the Human Genome Project

The Human Genome Project is one of the most important biomedical research projects of the 20th Century. It aimed to sequence all the human genome and DNA, and by 2003, the Human Genome Project had generated the first sequence of the human genome, accounting for over 90% of the information. By 2022, the sequence was finalised, but it only contained information about the female genome, with two X chromosomes. The Y chromosome was missing as it contains many repetitive sequences that are not transcribed to messenger RNA, making it difficult to assemble it fully. However, due to advancements in sequencing technology, a new study in 2023 published in Nature aimed to, for the first time, assemble complete sequences of multiple human Y chromosomes from 43 unrelated males around the world.

Sanger DNA sequencing method

DNA sequencing is a method used to determine the exact order of DNA bases (adenine, thymine, cytosine, and guanine) within a DNA molecule. Due to the aim of the Human Genome Project (to sequence all of the DNA), many methods were experimented with, leading to scientists ultimately refining, improving and using the Sanger DNA sequencing method. This method is the most accurate method for sequencing small fragments of DNA. It involves using patient DNA in a polymerase chain reaction (PCR). A mix of normal bases and chain-terminating bases is added. Chain-terminating bases stop DNA growth, creating fragments of different lengths, each ending in a terminator. The DNA fragments are separated by size through capillary gel electrophoresis. Each terminator base (adenine, thymine, cytosine, and guanine) has a different fluorescent tag. The fragments appear in order of length, and their fluorescent tags are recorded. This information is used to create a chromatograph, which is compared to a reference to identify variants, allowing DNA analysis.

Analysis of the Y chromosome

In 2023, a study published in Nature assembled complete sequences of multiple human Y chromosomes from 43 unrelated males around the world. The study discovered a high level of structural variation across the Y chromosomes, which was unexpected. The analysis showed a high level of diversity of the Y chromosome, and it is the beginning of the exploration of male genetic diversity. The study highlights that the information gained can be used in various fields of biomedicine, such as to gain more insight into the function and evolution of the human genome and to understand more about Y chromosome variants. This discovery can also lead to improved genetic testing accuracy and targeted treatments for personalised medicine.

Written by Naoshin Haque

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